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Largest ever review of new daily persistent headache assesses its clinical features
according to a new retrospective chart review.
“Future prospective studies are needed to better understand this disabling disorder,” wrote Randolph W. Evans, MD, of Baylor College of Medicine of Houston, and Dana P. Turner, PhD, of Massachusetts General Hospital and Harvard Medical School in Boston. Their study was published Oct. 28 in Headache.
To categorize the infrequently reported clinical features of NDPH, the researchers launched a retrospective study of patients who were provisionally diagnosed with NDPH by Dr. Evans at an outpatient clinic in Houston from Sept. 1, 2011, to Feb. 28, 2020. Of the 328 patients whose diagnosis ultimately matched the ICHD-3 criteria, the average age at onset was 40.3 years (range 12-87 years). Approximately 70% were White, and nearly 66% were women. Two hundred and sixty were diagnosed with the migraine phenotype and 68 were diagnosed with the tension-type phenotype.
Key features
The median duration of NDPH at the time of the initial consult with Dr. Evans was 0.7 years, and it was 1.9 years at the time of the last visit. Almost 33% of patients with the migraine phenotype had a history of episodic migraine compared with 16.2% with the tension-type phenotype. Headaches were side-locked unilateral in 8.5% (n = 28) of all patients, and 3.6% (n = 12) had a thunderclap onset.
The most common clinical features across all patients included noise sensitivity (72.1%), light sensitivity (71%), moderate pain at the time of initial consult (57.9%), pressure pain (54.9%), and throbbing pain (50.9%). Nausea was reported in 157 patients and vomiting was reported in 48 patients, all of whom were in the migraine phenotype group. Thunderclap onset was far more prevalent in the migraine phenotype group (11 patients) compared with the tension-type phenotype group (1 patient), as was vertigo (19 patients compared with 1) and visual aura (21 compared with 0).
The top precipitating factors across all patients included stressful life events (20.4%), an antecedent upper respiratory infection or flu-like illness (10.1%), and antecedent extracranial surgery (1.5%). Exacerbating or aggravating factors were far more prevalent in the migraine phenotype group compared with the tension-type phenotype group, with stress (14.6% vs. 5.9%), bright or flashing light (10.4% vs. 1.5%), loud noise (8.5% vs. 0%), and lack of sleep (6.5% vs. 4.4%) leading the way.
The months with the most onsets were June (8.5%), January (7.6%), and February (7.6%); there was no clear seasonal or cyclical variation. The most common prognostic type across all patients was persisting (refractory) at 93%, followed by remitting (self-limiting) at 4.3% and relapsing-remitting at 2.7%.
Unlocking a medical mystery
“This is the largest case review study ever published on NDPH, especially because most people think it’s a fairly rare disorder when it’s actually not,” Herbert G. Markley, MD, of the New England Regional Headache Center in Worcester, Mass., said in an interview.
“The thing people need to understand is that they may have a lot of these patients in their practice and not realize it,” he added. “They keep trying one medication after another, and the patients are giving up, and the doctors are giving up. It’s terrible. We don’t know what causes it, and we don’t know how to treat it. It’s one of the biggest mysteries left in medical science.”
“My idea about this condition, and this is shared by others, is that NDPH is not a diagnosis that describes a cohesive group of patients but rather a group of people who share certain features,” Morris Levin, MD, director of the Headache Center at the University of California, San Francisco, said in an interview. “And they would be better served if this diagnosis was split into different categories.”
While praising Dr. Evans and Dr. Turner for their categorization and classification work, Dr. Levin asked, “Let’s say you diagnose someone with NDPH; does that in any way help you with management of this person? The answer is no. Some might say, ‘If you put the patients in the migraine phenotype group, then you can use migraine treatments.’ My point would be: then call it migraine.
“I believe another way to approach NDPH might be to create subcategories of migraine and tension-type headaches,” he added. “A migraine that is either intermittent or nonexistent suddenly becomes daily. That could be a subcategory; rather than being called NDPH, call it ‘new persistent chronic migraine.’ Or ‘new persistent chronic tension-type headache.’ Perhaps that would serve us better in terms of grasping the underlying mechanisms and the best treatment for these patients.”
Along the same lines, Dr. Markley echoed Dr. Evans’ call for more prospective studies and more research on possible medication, hoping to fuel further understanding of this debilitating disorder.
“I think this will be a landmark study for people to look back on,” he said, “especially for anyone going into the headache specialty who has never heard of this type of headache and keeps wondering why they can’t help certain patients, no matter how many medications they try.”
The authors acknowledged their study’s limitations, including its single-center nature and the data abstraction process being performed by just one person. They added, however, that Dr. Evans is a “very experienced researcher with more than 30 years of experience in headache medicine who was abstracting his own patients, data that were very familiar to him.”
Dr. Evans and Dr. Turner declared no potential conflicts of interest.
according to a new retrospective chart review.
“Future prospective studies are needed to better understand this disabling disorder,” wrote Randolph W. Evans, MD, of Baylor College of Medicine of Houston, and Dana P. Turner, PhD, of Massachusetts General Hospital and Harvard Medical School in Boston. Their study was published Oct. 28 in Headache.
To categorize the infrequently reported clinical features of NDPH, the researchers launched a retrospective study of patients who were provisionally diagnosed with NDPH by Dr. Evans at an outpatient clinic in Houston from Sept. 1, 2011, to Feb. 28, 2020. Of the 328 patients whose diagnosis ultimately matched the ICHD-3 criteria, the average age at onset was 40.3 years (range 12-87 years). Approximately 70% were White, and nearly 66% were women. Two hundred and sixty were diagnosed with the migraine phenotype and 68 were diagnosed with the tension-type phenotype.
Key features
The median duration of NDPH at the time of the initial consult with Dr. Evans was 0.7 years, and it was 1.9 years at the time of the last visit. Almost 33% of patients with the migraine phenotype had a history of episodic migraine compared with 16.2% with the tension-type phenotype. Headaches were side-locked unilateral in 8.5% (n = 28) of all patients, and 3.6% (n = 12) had a thunderclap onset.
The most common clinical features across all patients included noise sensitivity (72.1%), light sensitivity (71%), moderate pain at the time of initial consult (57.9%), pressure pain (54.9%), and throbbing pain (50.9%). Nausea was reported in 157 patients and vomiting was reported in 48 patients, all of whom were in the migraine phenotype group. Thunderclap onset was far more prevalent in the migraine phenotype group (11 patients) compared with the tension-type phenotype group (1 patient), as was vertigo (19 patients compared with 1) and visual aura (21 compared with 0).
The top precipitating factors across all patients included stressful life events (20.4%), an antecedent upper respiratory infection or flu-like illness (10.1%), and antecedent extracranial surgery (1.5%). Exacerbating or aggravating factors were far more prevalent in the migraine phenotype group compared with the tension-type phenotype group, with stress (14.6% vs. 5.9%), bright or flashing light (10.4% vs. 1.5%), loud noise (8.5% vs. 0%), and lack of sleep (6.5% vs. 4.4%) leading the way.
The months with the most onsets were June (8.5%), January (7.6%), and February (7.6%); there was no clear seasonal or cyclical variation. The most common prognostic type across all patients was persisting (refractory) at 93%, followed by remitting (self-limiting) at 4.3% and relapsing-remitting at 2.7%.
Unlocking a medical mystery
“This is the largest case review study ever published on NDPH, especially because most people think it’s a fairly rare disorder when it’s actually not,” Herbert G. Markley, MD, of the New England Regional Headache Center in Worcester, Mass., said in an interview.
“The thing people need to understand is that they may have a lot of these patients in their practice and not realize it,” he added. “They keep trying one medication after another, and the patients are giving up, and the doctors are giving up. It’s terrible. We don’t know what causes it, and we don’t know how to treat it. It’s one of the biggest mysteries left in medical science.”
“My idea about this condition, and this is shared by others, is that NDPH is not a diagnosis that describes a cohesive group of patients but rather a group of people who share certain features,” Morris Levin, MD, director of the Headache Center at the University of California, San Francisco, said in an interview. “And they would be better served if this diagnosis was split into different categories.”
While praising Dr. Evans and Dr. Turner for their categorization and classification work, Dr. Levin asked, “Let’s say you diagnose someone with NDPH; does that in any way help you with management of this person? The answer is no. Some might say, ‘If you put the patients in the migraine phenotype group, then you can use migraine treatments.’ My point would be: then call it migraine.
“I believe another way to approach NDPH might be to create subcategories of migraine and tension-type headaches,” he added. “A migraine that is either intermittent or nonexistent suddenly becomes daily. That could be a subcategory; rather than being called NDPH, call it ‘new persistent chronic migraine.’ Or ‘new persistent chronic tension-type headache.’ Perhaps that would serve us better in terms of grasping the underlying mechanisms and the best treatment for these patients.”
Along the same lines, Dr. Markley echoed Dr. Evans’ call for more prospective studies and more research on possible medication, hoping to fuel further understanding of this debilitating disorder.
“I think this will be a landmark study for people to look back on,” he said, “especially for anyone going into the headache specialty who has never heard of this type of headache and keeps wondering why they can’t help certain patients, no matter how many medications they try.”
The authors acknowledged their study’s limitations, including its single-center nature and the data abstraction process being performed by just one person. They added, however, that Dr. Evans is a “very experienced researcher with more than 30 years of experience in headache medicine who was abstracting his own patients, data that were very familiar to him.”
Dr. Evans and Dr. Turner declared no potential conflicts of interest.
according to a new retrospective chart review.
“Future prospective studies are needed to better understand this disabling disorder,” wrote Randolph W. Evans, MD, of Baylor College of Medicine of Houston, and Dana P. Turner, PhD, of Massachusetts General Hospital and Harvard Medical School in Boston. Their study was published Oct. 28 in Headache.
To categorize the infrequently reported clinical features of NDPH, the researchers launched a retrospective study of patients who were provisionally diagnosed with NDPH by Dr. Evans at an outpatient clinic in Houston from Sept. 1, 2011, to Feb. 28, 2020. Of the 328 patients whose diagnosis ultimately matched the ICHD-3 criteria, the average age at onset was 40.3 years (range 12-87 years). Approximately 70% were White, and nearly 66% were women. Two hundred and sixty were diagnosed with the migraine phenotype and 68 were diagnosed with the tension-type phenotype.
Key features
The median duration of NDPH at the time of the initial consult with Dr. Evans was 0.7 years, and it was 1.9 years at the time of the last visit. Almost 33% of patients with the migraine phenotype had a history of episodic migraine compared with 16.2% with the tension-type phenotype. Headaches were side-locked unilateral in 8.5% (n = 28) of all patients, and 3.6% (n = 12) had a thunderclap onset.
The most common clinical features across all patients included noise sensitivity (72.1%), light sensitivity (71%), moderate pain at the time of initial consult (57.9%), pressure pain (54.9%), and throbbing pain (50.9%). Nausea was reported in 157 patients and vomiting was reported in 48 patients, all of whom were in the migraine phenotype group. Thunderclap onset was far more prevalent in the migraine phenotype group (11 patients) compared with the tension-type phenotype group (1 patient), as was vertigo (19 patients compared with 1) and visual aura (21 compared with 0).
The top precipitating factors across all patients included stressful life events (20.4%), an antecedent upper respiratory infection or flu-like illness (10.1%), and antecedent extracranial surgery (1.5%). Exacerbating or aggravating factors were far more prevalent in the migraine phenotype group compared with the tension-type phenotype group, with stress (14.6% vs. 5.9%), bright or flashing light (10.4% vs. 1.5%), loud noise (8.5% vs. 0%), and lack of sleep (6.5% vs. 4.4%) leading the way.
The months with the most onsets were June (8.5%), January (7.6%), and February (7.6%); there was no clear seasonal or cyclical variation. The most common prognostic type across all patients was persisting (refractory) at 93%, followed by remitting (self-limiting) at 4.3% and relapsing-remitting at 2.7%.
Unlocking a medical mystery
“This is the largest case review study ever published on NDPH, especially because most people think it’s a fairly rare disorder when it’s actually not,” Herbert G. Markley, MD, of the New England Regional Headache Center in Worcester, Mass., said in an interview.
“The thing people need to understand is that they may have a lot of these patients in their practice and not realize it,” he added. “They keep trying one medication after another, and the patients are giving up, and the doctors are giving up. It’s terrible. We don’t know what causes it, and we don’t know how to treat it. It’s one of the biggest mysteries left in medical science.”
“My idea about this condition, and this is shared by others, is that NDPH is not a diagnosis that describes a cohesive group of patients but rather a group of people who share certain features,” Morris Levin, MD, director of the Headache Center at the University of California, San Francisco, said in an interview. “And they would be better served if this diagnosis was split into different categories.”
While praising Dr. Evans and Dr. Turner for their categorization and classification work, Dr. Levin asked, “Let’s say you diagnose someone with NDPH; does that in any way help you with management of this person? The answer is no. Some might say, ‘If you put the patients in the migraine phenotype group, then you can use migraine treatments.’ My point would be: then call it migraine.
“I believe another way to approach NDPH might be to create subcategories of migraine and tension-type headaches,” he added. “A migraine that is either intermittent or nonexistent suddenly becomes daily. That could be a subcategory; rather than being called NDPH, call it ‘new persistent chronic migraine.’ Or ‘new persistent chronic tension-type headache.’ Perhaps that would serve us better in terms of grasping the underlying mechanisms and the best treatment for these patients.”
Along the same lines, Dr. Markley echoed Dr. Evans’ call for more prospective studies and more research on possible medication, hoping to fuel further understanding of this debilitating disorder.
“I think this will be a landmark study for people to look back on,” he said, “especially for anyone going into the headache specialty who has never heard of this type of headache and keeps wondering why they can’t help certain patients, no matter how many medications they try.”
The authors acknowledged their study’s limitations, including its single-center nature and the data abstraction process being performed by just one person. They added, however, that Dr. Evans is a “very experienced researcher with more than 30 years of experience in headache medicine who was abstracting his own patients, data that were very familiar to him.”
Dr. Evans and Dr. Turner declared no potential conflicts of interest.
FROM HEADACHE
DIY nerve stimulation effective in episodic migraine
results from a phase 3 study show.
This is great news for headache patients who want to explore nondrug treatment options, said study investigator Deena E. Kuruvilla, MD, neurologist and headache specialist at the Westport Headache Institute, Connecticut.
She added that such devices “aren’t always part of the conversation when we’re discussing preventive and acute treatments with our patients. Making this a regular part of the conversation might be helpful to patients.”
The findings were presented at ANA 2021: 146th Annual Meeting of the American Neurological Association (ANA), which was held online.
A key therapeutic target
The randomized, double-blind trial compared E-TNS with sham stimulation for the acute treatment of migraine.
The E-TNS device (Verum Cefaly Abortive Program) stimulates the supraorbital nerve in the forehead. “This nerve is a branch of the trigeminal nerve, which is thought to be the key player in migraine pathophysiology,” Dr. Kuruvilla noted.
The device has been cleared by the U.S. Food and Drug Administration for acute and preventive treatment of migraine.
During a run-in period before randomization, patients were asked to keep a detailed headache diary and to become comfortable using the trial device to treat an acute migraine attack at home.
The study enrolled 538 adult patients at 10 centers. The patients were aged 18 to 65 years, and they had been having episodic migraines, with or without aura, for at least a year. The participants had to have received a migraine diagnosis before age 50, and they had to be experiencing an attack of migraine 2 to 8 days per month.
The patients used the device only for a migraine of at least moderate intensity that was accompanied by at least one migraine-associated symptom, such as photophobia, phonophobia, or nausea. They were asked not to take rescue medication prior to or during a therapy session.
Study participants applied either neurostimulation or sham stimulation for a continuous 2-hour period within 4 hours of a migraine attack over the 2-month study period.
The two primary endpoints were pain freedom and freedom from the most bothersome migraine-associated symptoms at 2 hours.
Compared to sham treatment, active stimulation was more effective in achieving pain freedom (P = .043) and freedom from the most bothersome migraine-associated symptom (P = .001) at 2 hours.
“So the study did meet both primary endpoints with statistical significance,” said Dr. Kuruvilla.
The five secondary endpoints included pain relief at 2 hours; absence of all migraine-associated symptoms at 2 hours; use of rescue medication within 24 hours; sustained pain freedom at 24 hours; and sustained pain relief at 24 hours.
All but one of these endpoints reached statistical significance, showing superiority for the active intervention. The only exception was in regard to use of rescue medication.
The most common adverse event (AE) was forehead paresthesia, discomfort, or burning, which was more common in the active-treatment group than in the sham-treatment group (P = .009). There were four cases of nausea or vomiting in the active-treatment group and none in the sham-treatment group. There were no serious AEs.
Available over the counter
Both moderators of the headache poster tour that featured this study – Justin C. McArthur, MBBS, from Johns Hopkins University, Baltimore, and Steven Galetta, MD, from NYU Grossman School of Medicine – praised the presentation.
Dr. Galetta questioned whether patients were receiving preventive therapies. Dr. Kuruvilla said that the patients were allowed to enter the trial while taking preventive therapies, including antiepileptic treatments, blood pressure medications, and antidepressants, but that they had to be receiving stable doses.
The investigators didn’t distinguish between participants who were taking preventive therapies and those who weren’t, she said. “The aim was really to look at acute treatment for migraine,” and patients taking such medication “had been stable on their regimen for a pretty prolonged period of time.”
Dr. McArthur asked about the origin of the nausea some patients experienced.
It was difficult to determine whether the nausea was an aspect of an individual patient’s migraine attack or was an effect of the stimulation, said Dr. Kuruvilla. She noted that some patients found the vibrating sensation from the device uncomfortable and that nausea could be associated with pain at the site.
The device costs $300 to $400 (U.S.) and is available over the counter.
Dr. Kuruvilla is a consultant for Cefaly, Neurolief, Theranica, Now What Media, and Kx Advisors. She is on the speakers bureau for AbbVie/Allergan, Amgen/Novartis, Lilly, the American Headache Society, Biohaven, and CME meeting, and she is on an advisory board at AbbVie/Allergan, Lilly, Theranica, and Amgen/Novartis. She is editor and associate editor of Healthline and is an author for WebMD/Medscape, Healthline.
A version of this article first appeared on Medscape.com.
results from a phase 3 study show.
This is great news for headache patients who want to explore nondrug treatment options, said study investigator Deena E. Kuruvilla, MD, neurologist and headache specialist at the Westport Headache Institute, Connecticut.
She added that such devices “aren’t always part of the conversation when we’re discussing preventive and acute treatments with our patients. Making this a regular part of the conversation might be helpful to patients.”
The findings were presented at ANA 2021: 146th Annual Meeting of the American Neurological Association (ANA), which was held online.
A key therapeutic target
The randomized, double-blind trial compared E-TNS with sham stimulation for the acute treatment of migraine.
The E-TNS device (Verum Cefaly Abortive Program) stimulates the supraorbital nerve in the forehead. “This nerve is a branch of the trigeminal nerve, which is thought to be the key player in migraine pathophysiology,” Dr. Kuruvilla noted.
The device has been cleared by the U.S. Food and Drug Administration for acute and preventive treatment of migraine.
During a run-in period before randomization, patients were asked to keep a detailed headache diary and to become comfortable using the trial device to treat an acute migraine attack at home.
The study enrolled 538 adult patients at 10 centers. The patients were aged 18 to 65 years, and they had been having episodic migraines, with or without aura, for at least a year. The participants had to have received a migraine diagnosis before age 50, and they had to be experiencing an attack of migraine 2 to 8 days per month.
The patients used the device only for a migraine of at least moderate intensity that was accompanied by at least one migraine-associated symptom, such as photophobia, phonophobia, or nausea. They were asked not to take rescue medication prior to or during a therapy session.
Study participants applied either neurostimulation or sham stimulation for a continuous 2-hour period within 4 hours of a migraine attack over the 2-month study period.
The two primary endpoints were pain freedom and freedom from the most bothersome migraine-associated symptoms at 2 hours.
Compared to sham treatment, active stimulation was more effective in achieving pain freedom (P = .043) and freedom from the most bothersome migraine-associated symptom (P = .001) at 2 hours.
“So the study did meet both primary endpoints with statistical significance,” said Dr. Kuruvilla.
The five secondary endpoints included pain relief at 2 hours; absence of all migraine-associated symptoms at 2 hours; use of rescue medication within 24 hours; sustained pain freedom at 24 hours; and sustained pain relief at 24 hours.
All but one of these endpoints reached statistical significance, showing superiority for the active intervention. The only exception was in regard to use of rescue medication.
The most common adverse event (AE) was forehead paresthesia, discomfort, or burning, which was more common in the active-treatment group than in the sham-treatment group (P = .009). There were four cases of nausea or vomiting in the active-treatment group and none in the sham-treatment group. There were no serious AEs.
Available over the counter
Both moderators of the headache poster tour that featured this study – Justin C. McArthur, MBBS, from Johns Hopkins University, Baltimore, and Steven Galetta, MD, from NYU Grossman School of Medicine – praised the presentation.
Dr. Galetta questioned whether patients were receiving preventive therapies. Dr. Kuruvilla said that the patients were allowed to enter the trial while taking preventive therapies, including antiepileptic treatments, blood pressure medications, and antidepressants, but that they had to be receiving stable doses.
The investigators didn’t distinguish between participants who were taking preventive therapies and those who weren’t, she said. “The aim was really to look at acute treatment for migraine,” and patients taking such medication “had been stable on their regimen for a pretty prolonged period of time.”
Dr. McArthur asked about the origin of the nausea some patients experienced.
It was difficult to determine whether the nausea was an aspect of an individual patient’s migraine attack or was an effect of the stimulation, said Dr. Kuruvilla. She noted that some patients found the vibrating sensation from the device uncomfortable and that nausea could be associated with pain at the site.
The device costs $300 to $400 (U.S.) and is available over the counter.
Dr. Kuruvilla is a consultant for Cefaly, Neurolief, Theranica, Now What Media, and Kx Advisors. She is on the speakers bureau for AbbVie/Allergan, Amgen/Novartis, Lilly, the American Headache Society, Biohaven, and CME meeting, and she is on an advisory board at AbbVie/Allergan, Lilly, Theranica, and Amgen/Novartis. She is editor and associate editor of Healthline and is an author for WebMD/Medscape, Healthline.
A version of this article first appeared on Medscape.com.
results from a phase 3 study show.
This is great news for headache patients who want to explore nondrug treatment options, said study investigator Deena E. Kuruvilla, MD, neurologist and headache specialist at the Westport Headache Institute, Connecticut.
She added that such devices “aren’t always part of the conversation when we’re discussing preventive and acute treatments with our patients. Making this a regular part of the conversation might be helpful to patients.”
The findings were presented at ANA 2021: 146th Annual Meeting of the American Neurological Association (ANA), which was held online.
A key therapeutic target
The randomized, double-blind trial compared E-TNS with sham stimulation for the acute treatment of migraine.
The E-TNS device (Verum Cefaly Abortive Program) stimulates the supraorbital nerve in the forehead. “This nerve is a branch of the trigeminal nerve, which is thought to be the key player in migraine pathophysiology,” Dr. Kuruvilla noted.
The device has been cleared by the U.S. Food and Drug Administration for acute and preventive treatment of migraine.
During a run-in period before randomization, patients were asked to keep a detailed headache diary and to become comfortable using the trial device to treat an acute migraine attack at home.
The study enrolled 538 adult patients at 10 centers. The patients were aged 18 to 65 years, and they had been having episodic migraines, with or without aura, for at least a year. The participants had to have received a migraine diagnosis before age 50, and they had to be experiencing an attack of migraine 2 to 8 days per month.
The patients used the device only for a migraine of at least moderate intensity that was accompanied by at least one migraine-associated symptom, such as photophobia, phonophobia, or nausea. They were asked not to take rescue medication prior to or during a therapy session.
Study participants applied either neurostimulation or sham stimulation for a continuous 2-hour period within 4 hours of a migraine attack over the 2-month study period.
The two primary endpoints were pain freedom and freedom from the most bothersome migraine-associated symptoms at 2 hours.
Compared to sham treatment, active stimulation was more effective in achieving pain freedom (P = .043) and freedom from the most bothersome migraine-associated symptom (P = .001) at 2 hours.
“So the study did meet both primary endpoints with statistical significance,” said Dr. Kuruvilla.
The five secondary endpoints included pain relief at 2 hours; absence of all migraine-associated symptoms at 2 hours; use of rescue medication within 24 hours; sustained pain freedom at 24 hours; and sustained pain relief at 24 hours.
All but one of these endpoints reached statistical significance, showing superiority for the active intervention. The only exception was in regard to use of rescue medication.
The most common adverse event (AE) was forehead paresthesia, discomfort, or burning, which was more common in the active-treatment group than in the sham-treatment group (P = .009). There were four cases of nausea or vomiting in the active-treatment group and none in the sham-treatment group. There were no serious AEs.
Available over the counter
Both moderators of the headache poster tour that featured this study – Justin C. McArthur, MBBS, from Johns Hopkins University, Baltimore, and Steven Galetta, MD, from NYU Grossman School of Medicine – praised the presentation.
Dr. Galetta questioned whether patients were receiving preventive therapies. Dr. Kuruvilla said that the patients were allowed to enter the trial while taking preventive therapies, including antiepileptic treatments, blood pressure medications, and antidepressants, but that they had to be receiving stable doses.
The investigators didn’t distinguish between participants who were taking preventive therapies and those who weren’t, she said. “The aim was really to look at acute treatment for migraine,” and patients taking such medication “had been stable on their regimen for a pretty prolonged period of time.”
Dr. McArthur asked about the origin of the nausea some patients experienced.
It was difficult to determine whether the nausea was an aspect of an individual patient’s migraine attack or was an effect of the stimulation, said Dr. Kuruvilla. She noted that some patients found the vibrating sensation from the device uncomfortable and that nausea could be associated with pain at the site.
The device costs $300 to $400 (U.S.) and is available over the counter.
Dr. Kuruvilla is a consultant for Cefaly, Neurolief, Theranica, Now What Media, and Kx Advisors. She is on the speakers bureau for AbbVie/Allergan, Amgen/Novartis, Lilly, the American Headache Society, Biohaven, and CME meeting, and she is on an advisory board at AbbVie/Allergan, Lilly, Theranica, and Amgen/Novartis. She is editor and associate editor of Healthline and is an author for WebMD/Medscape, Healthline.
A version of this article first appeared on Medscape.com.
FROM ANA
Pandemic survey: Forty-six percent of pediatric headache patients got worse
, a newly released survey finds. But some actually found the pandemic era to be less stressful since they were tightly wound and could more easily control their home environments, a researcher said.
“We need to be very mindful of the connections between school and home environments – and social situations – and how they impact headache frequency,” said Marc DiSabella, DO, a pediatric neurologist at Children’s National Hospital/George Washington University, Washington. He is coauthor of a poster presented at the 50th annual meeting of the Child Neurology Society.
Dr. DiSabella and colleagues launched the survey to understand what headache patients were experiencing during the pandemic. They expected that “things were going to go really terrible in terms of headaches – or things would go great, and then things would crash when we had to reintegrate into society,” he said in an interview.
The team surveyed 113 pediatric patients who were evaluated at the hospital’s headache clinic between summer 2020 and winter 2021. Most of the patients were female (60%) and were aged 12-17 years (63%). Twenty-one percent were younger than 12 and 16% were older than 17. Chronic migraine (37%) was the most common diagnosis, followed by migraine with aura (22%), migraine without aura (19%), and new daily persistent headache (15%).
Nearly half (46%) of patients said their headaches had worsened during the pandemic. Many also reported more anxiety (55%), worsened mood (48%) and more stress (55%).
Dr. DiSabella said it’s especially notable that nearly two-thirds of those surveyed reported they were exercising less during the pandemic. Research has suggested that exercise and proper diet/sleep are crucial to improving headaches in kids, he said, and the survey findings suggest that exercise may be especially important. “Engaging in physical activity changes their pain threshold,” he said.
The researchers also reported that 60% of those surveyed said they looked at screens more than 6 hours per day. According to Dr. DiSabella, high screen use may not be worrisome from a headache perspective. “We have another study in publication that shows there’s not a clear association between frequency of screen use and headache intensity,” he said.
The survey doesn’t examine what has happened in recent weeks as schools have reopened. Anecdotally, Dr. DiSabella said some patients with migraine are feeling the stress of returning to normal routines. “They tend to be type A perfectionists and do well when they’re in control of their environment,” he said. “Now they’ve lost the control they had at home and are being put back into a stressful environment.”
Pandemic effects mixed
Commenting on the study, child neurologist Andrew D. Hershey, MD, PhD, of Cincinnati Children’s Hospital Medical Center, questioned the finding that many children suffered from more headaches during the pandemic. In his experience, “headaches were overall better when [children] were doing virtual learning,” he said in an interview. “We had fewer admissions, ED visits declined, and patients were maintaining better healthy habits. Some did express anxiety about not seeing friends, but were accommodating by doing this remotely.”
He added: “Since their return, kids are back to the same sleep deprivation issue since schools start too early, and they have more difficulty treating headaches acutely since they have to go to the nurse’s office [to do so]. They self-report a higher degree of stress and anxiety.”
On the other hand, Jack Gladstein, MD, a child neurologist at the University of Maryland, Baltimore, said in an interview that most of his patients suffered more headaches during the pandemic, although a small number with social anxiety thrived because they got to stay at home.
He agreed with Dr. DiSabella about the value of exercise. “At every visit we remind our youngsters with migraine to eat breakfast, exercise, get regular sleep, and drink fluids,” he said.
No study funding was reported. The study authors, Dr. Hershey, and Dr. Gladstein reported no disclosures.
, a newly released survey finds. But some actually found the pandemic era to be less stressful since they were tightly wound and could more easily control their home environments, a researcher said.
“We need to be very mindful of the connections between school and home environments – and social situations – and how they impact headache frequency,” said Marc DiSabella, DO, a pediatric neurologist at Children’s National Hospital/George Washington University, Washington. He is coauthor of a poster presented at the 50th annual meeting of the Child Neurology Society.
Dr. DiSabella and colleagues launched the survey to understand what headache patients were experiencing during the pandemic. They expected that “things were going to go really terrible in terms of headaches – or things would go great, and then things would crash when we had to reintegrate into society,” he said in an interview.
The team surveyed 113 pediatric patients who were evaluated at the hospital’s headache clinic between summer 2020 and winter 2021. Most of the patients were female (60%) and were aged 12-17 years (63%). Twenty-one percent were younger than 12 and 16% were older than 17. Chronic migraine (37%) was the most common diagnosis, followed by migraine with aura (22%), migraine without aura (19%), and new daily persistent headache (15%).
Nearly half (46%) of patients said their headaches had worsened during the pandemic. Many also reported more anxiety (55%), worsened mood (48%) and more stress (55%).
Dr. DiSabella said it’s especially notable that nearly two-thirds of those surveyed reported they were exercising less during the pandemic. Research has suggested that exercise and proper diet/sleep are crucial to improving headaches in kids, he said, and the survey findings suggest that exercise may be especially important. “Engaging in physical activity changes their pain threshold,” he said.
The researchers also reported that 60% of those surveyed said they looked at screens more than 6 hours per day. According to Dr. DiSabella, high screen use may not be worrisome from a headache perspective. “We have another study in publication that shows there’s not a clear association between frequency of screen use and headache intensity,” he said.
The survey doesn’t examine what has happened in recent weeks as schools have reopened. Anecdotally, Dr. DiSabella said some patients with migraine are feeling the stress of returning to normal routines. “They tend to be type A perfectionists and do well when they’re in control of their environment,” he said. “Now they’ve lost the control they had at home and are being put back into a stressful environment.”
Pandemic effects mixed
Commenting on the study, child neurologist Andrew D. Hershey, MD, PhD, of Cincinnati Children’s Hospital Medical Center, questioned the finding that many children suffered from more headaches during the pandemic. In his experience, “headaches were overall better when [children] were doing virtual learning,” he said in an interview. “We had fewer admissions, ED visits declined, and patients were maintaining better healthy habits. Some did express anxiety about not seeing friends, but were accommodating by doing this remotely.”
He added: “Since their return, kids are back to the same sleep deprivation issue since schools start too early, and they have more difficulty treating headaches acutely since they have to go to the nurse’s office [to do so]. They self-report a higher degree of stress and anxiety.”
On the other hand, Jack Gladstein, MD, a child neurologist at the University of Maryland, Baltimore, said in an interview that most of his patients suffered more headaches during the pandemic, although a small number with social anxiety thrived because they got to stay at home.
He agreed with Dr. DiSabella about the value of exercise. “At every visit we remind our youngsters with migraine to eat breakfast, exercise, get regular sleep, and drink fluids,” he said.
No study funding was reported. The study authors, Dr. Hershey, and Dr. Gladstein reported no disclosures.
, a newly released survey finds. But some actually found the pandemic era to be less stressful since they were tightly wound and could more easily control their home environments, a researcher said.
“We need to be very mindful of the connections between school and home environments – and social situations – and how they impact headache frequency,” said Marc DiSabella, DO, a pediatric neurologist at Children’s National Hospital/George Washington University, Washington. He is coauthor of a poster presented at the 50th annual meeting of the Child Neurology Society.
Dr. DiSabella and colleagues launched the survey to understand what headache patients were experiencing during the pandemic. They expected that “things were going to go really terrible in terms of headaches – or things would go great, and then things would crash when we had to reintegrate into society,” he said in an interview.
The team surveyed 113 pediatric patients who were evaluated at the hospital’s headache clinic between summer 2020 and winter 2021. Most of the patients were female (60%) and were aged 12-17 years (63%). Twenty-one percent were younger than 12 and 16% were older than 17. Chronic migraine (37%) was the most common diagnosis, followed by migraine with aura (22%), migraine without aura (19%), and new daily persistent headache (15%).
Nearly half (46%) of patients said their headaches had worsened during the pandemic. Many also reported more anxiety (55%), worsened mood (48%) and more stress (55%).
Dr. DiSabella said it’s especially notable that nearly two-thirds of those surveyed reported they were exercising less during the pandemic. Research has suggested that exercise and proper diet/sleep are crucial to improving headaches in kids, he said, and the survey findings suggest that exercise may be especially important. “Engaging in physical activity changes their pain threshold,” he said.
The researchers also reported that 60% of those surveyed said they looked at screens more than 6 hours per day. According to Dr. DiSabella, high screen use may not be worrisome from a headache perspective. “We have another study in publication that shows there’s not a clear association between frequency of screen use and headache intensity,” he said.
The survey doesn’t examine what has happened in recent weeks as schools have reopened. Anecdotally, Dr. DiSabella said some patients with migraine are feeling the stress of returning to normal routines. “They tend to be type A perfectionists and do well when they’re in control of their environment,” he said. “Now they’ve lost the control they had at home and are being put back into a stressful environment.”
Pandemic effects mixed
Commenting on the study, child neurologist Andrew D. Hershey, MD, PhD, of Cincinnati Children’s Hospital Medical Center, questioned the finding that many children suffered from more headaches during the pandemic. In his experience, “headaches were overall better when [children] were doing virtual learning,” he said in an interview. “We had fewer admissions, ED visits declined, and patients were maintaining better healthy habits. Some did express anxiety about not seeing friends, but were accommodating by doing this remotely.”
He added: “Since their return, kids are back to the same sleep deprivation issue since schools start too early, and they have more difficulty treating headaches acutely since they have to go to the nurse’s office [to do so]. They self-report a higher degree of stress and anxiety.”
On the other hand, Jack Gladstein, MD, a child neurologist at the University of Maryland, Baltimore, said in an interview that most of his patients suffered more headaches during the pandemic, although a small number with social anxiety thrived because they got to stay at home.
He agreed with Dr. DiSabella about the value of exercise. “At every visit we remind our youngsters with migraine to eat breakfast, exercise, get regular sleep, and drink fluids,” he said.
No study funding was reported. The study authors, Dr. Hershey, and Dr. Gladstein reported no disclosures.
FROM CNS 2021
FDA okays new oral CGRP antagonist for migraine prevention
the manufacturer announced in a release.
The once-daily medication will be available in doses of 10 mg, 30 mg, and 60 mg.
“Qulipta provides a simple oral treatment option specifically developed to prevent migraine attacks and target CGRP, which is believed to be crucially involved in migraine in many patients,” coinvestigator Peter J. Goadsby, MD, PhD, DSc, neurologist and professor at the University of California, Los Angeles, and King’s College London, said in the release.
Approval was based partly on the findings from the phase 3 ADVANCE trial, in which patients with episodic migraine were randomly assigned to receive placebo or a 10-mg, 30-mg, or 60-mg daily dose of atogepant for 12 weeks.
As reported by this news organization, all three doses of atogepant reduced the number of mean monthly migraine days.
With this approval, neurologists will be able to choose from four monoclonal antibodies and two gepants for the preventive treatment of migraine.
“Having another gepant that can also be given preventively is a good idea, because one may be better than the other for a patient,” Alan M. Rapoport, MD, past president of the International Headache Society and founder and director emeritus of the New England Center for Headache, Stamford, Conn., told this news organization.
“Once we have a year or so of experience with atogepant, we’ll have a pretty good idea of which one works better preventively,” said Dr. Rapoport, who was not involved with the research.
Practice changing?
In the ADVANCE trial, there was a reduction of 3.69 migraine days with the 10-mg dose, 3.86 days with the 30-mg dose, and 4.2 days with the 60-mg dose. Placebo was associated with a reduction of 2.48 migraine days.
In addition, more than half of patients in each atogepant arm achieved a reduction in mean monthly migraine days of 50% or greater. This outcome occurred in 55.6% of the 10-mg atogepant group, 58.7% of the 30-mg group, and 60.8% of the 60-mg group. Approximately 29% patients who received placebo achieved this outcome.
The data indicated that atogepant has a favorable safety profile. The most common adverse events associated with treatment were constipation, nausea, and upper respiratory tract infection.
Dr. Rapoport, who is also a clinical professor of neurology at UCLA, noted that he was impressed with the efficacy.
“I’m not as impressed with the adverse events, but they’re not serious, and they don’t necessarily last,” he said.
Although being able to prescribe a single drug for acute and preventive treatment may be an advantage, it remains to be seen whether the tolerability and price of atogepant will be barriers for patients, Dr. Rapoport added.
How the approval will affect clinical practice is also unclear, he noted.
“If you’re going to start someone on a preventive, especially if it’s a woman of childbearing potential, you might just consider one of the two gepants. Doctors will decide once they see how they work,” said Dr. Rapoport.
Not a ‘breakthrough’ treatment
Also commenting ahead of the approval, Elizabeth W. Loder, MD, vice chair for academic affairs in the department of neurology at Brigham and Women’s Hospital, Boston, noted that the “safety of these CGRP medications in pregnancy is uncertain, and there are theoretical reasons to be concerned about it.”
Unlike injectable CGRP medications, atogepant is eliminated from the body relatively quickly after the patient stops taking it, said Dr. Loder, who is also professor of neurology at Harvard Medical School, Boston. However, atogepant may not otherwise differ greatly from other medications of its type.
“I don’t see a reason to think that one of these oral CGRP medicines is much more effective than another one,” said Dr. Loder.
“In my mind, as a clinician who will be prescribing these for patients, it will be cost and the ease of getting it covered that makes the difference,” she added.
These questions may raise concerns. “Those of us who treat patients who do not have private insurance find it very difficult to get these medications for them, even in situations where they have exhausted other alternatives,” said Dr. Loder.
Patients insured by Medicare or Medicaid “usually have no avenue to get some of these new, expensive treatments,” she said.
The approval of atogepant for acute and preventive treatment shows that the distinction between these indications may be artificial, Dr. Loder noted. The approval “will, I hope, help people think more flexibly about the way in which we use medications.”
It is a positive that atogepant has emerged as another option for preventive therapy, but the treatment cannot be considered a breakthrough, Dr. Loder added. The efficacy of atogepant, like that of other preventive treatments for migraine, is modest.
“It would be so nice if we could find things that were more effective than the treatments we currently have,” said Dr. Loder.
A version of this article first appeared on Medscape.com.
the manufacturer announced in a release.
The once-daily medication will be available in doses of 10 mg, 30 mg, and 60 mg.
“Qulipta provides a simple oral treatment option specifically developed to prevent migraine attacks and target CGRP, which is believed to be crucially involved in migraine in many patients,” coinvestigator Peter J. Goadsby, MD, PhD, DSc, neurologist and professor at the University of California, Los Angeles, and King’s College London, said in the release.
Approval was based partly on the findings from the phase 3 ADVANCE trial, in which patients with episodic migraine were randomly assigned to receive placebo or a 10-mg, 30-mg, or 60-mg daily dose of atogepant for 12 weeks.
As reported by this news organization, all three doses of atogepant reduced the number of mean monthly migraine days.
With this approval, neurologists will be able to choose from four monoclonal antibodies and two gepants for the preventive treatment of migraine.
“Having another gepant that can also be given preventively is a good idea, because one may be better than the other for a patient,” Alan M. Rapoport, MD, past president of the International Headache Society and founder and director emeritus of the New England Center for Headache, Stamford, Conn., told this news organization.
“Once we have a year or so of experience with atogepant, we’ll have a pretty good idea of which one works better preventively,” said Dr. Rapoport, who was not involved with the research.
Practice changing?
In the ADVANCE trial, there was a reduction of 3.69 migraine days with the 10-mg dose, 3.86 days with the 30-mg dose, and 4.2 days with the 60-mg dose. Placebo was associated with a reduction of 2.48 migraine days.
In addition, more than half of patients in each atogepant arm achieved a reduction in mean monthly migraine days of 50% or greater. This outcome occurred in 55.6% of the 10-mg atogepant group, 58.7% of the 30-mg group, and 60.8% of the 60-mg group. Approximately 29% patients who received placebo achieved this outcome.
The data indicated that atogepant has a favorable safety profile. The most common adverse events associated with treatment were constipation, nausea, and upper respiratory tract infection.
Dr. Rapoport, who is also a clinical professor of neurology at UCLA, noted that he was impressed with the efficacy.
“I’m not as impressed with the adverse events, but they’re not serious, and they don’t necessarily last,” he said.
Although being able to prescribe a single drug for acute and preventive treatment may be an advantage, it remains to be seen whether the tolerability and price of atogepant will be barriers for patients, Dr. Rapoport added.
How the approval will affect clinical practice is also unclear, he noted.
“If you’re going to start someone on a preventive, especially if it’s a woman of childbearing potential, you might just consider one of the two gepants. Doctors will decide once they see how they work,” said Dr. Rapoport.
Not a ‘breakthrough’ treatment
Also commenting ahead of the approval, Elizabeth W. Loder, MD, vice chair for academic affairs in the department of neurology at Brigham and Women’s Hospital, Boston, noted that the “safety of these CGRP medications in pregnancy is uncertain, and there are theoretical reasons to be concerned about it.”
Unlike injectable CGRP medications, atogepant is eliminated from the body relatively quickly after the patient stops taking it, said Dr. Loder, who is also professor of neurology at Harvard Medical School, Boston. However, atogepant may not otherwise differ greatly from other medications of its type.
“I don’t see a reason to think that one of these oral CGRP medicines is much more effective than another one,” said Dr. Loder.
“In my mind, as a clinician who will be prescribing these for patients, it will be cost and the ease of getting it covered that makes the difference,” she added.
These questions may raise concerns. “Those of us who treat patients who do not have private insurance find it very difficult to get these medications for them, even in situations where they have exhausted other alternatives,” said Dr. Loder.
Patients insured by Medicare or Medicaid “usually have no avenue to get some of these new, expensive treatments,” she said.
The approval of atogepant for acute and preventive treatment shows that the distinction between these indications may be artificial, Dr. Loder noted. The approval “will, I hope, help people think more flexibly about the way in which we use medications.”
It is a positive that atogepant has emerged as another option for preventive therapy, but the treatment cannot be considered a breakthrough, Dr. Loder added. The efficacy of atogepant, like that of other preventive treatments for migraine, is modest.
“It would be so nice if we could find things that were more effective than the treatments we currently have,” said Dr. Loder.
A version of this article first appeared on Medscape.com.
the manufacturer announced in a release.
The once-daily medication will be available in doses of 10 mg, 30 mg, and 60 mg.
“Qulipta provides a simple oral treatment option specifically developed to prevent migraine attacks and target CGRP, which is believed to be crucially involved in migraine in many patients,” coinvestigator Peter J. Goadsby, MD, PhD, DSc, neurologist and professor at the University of California, Los Angeles, and King’s College London, said in the release.
Approval was based partly on the findings from the phase 3 ADVANCE trial, in which patients with episodic migraine were randomly assigned to receive placebo or a 10-mg, 30-mg, or 60-mg daily dose of atogepant for 12 weeks.
As reported by this news organization, all three doses of atogepant reduced the number of mean monthly migraine days.
With this approval, neurologists will be able to choose from four monoclonal antibodies and two gepants for the preventive treatment of migraine.
“Having another gepant that can also be given preventively is a good idea, because one may be better than the other for a patient,” Alan M. Rapoport, MD, past president of the International Headache Society and founder and director emeritus of the New England Center for Headache, Stamford, Conn., told this news organization.
“Once we have a year or so of experience with atogepant, we’ll have a pretty good idea of which one works better preventively,” said Dr. Rapoport, who was not involved with the research.
Practice changing?
In the ADVANCE trial, there was a reduction of 3.69 migraine days with the 10-mg dose, 3.86 days with the 30-mg dose, and 4.2 days with the 60-mg dose. Placebo was associated with a reduction of 2.48 migraine days.
In addition, more than half of patients in each atogepant arm achieved a reduction in mean monthly migraine days of 50% or greater. This outcome occurred in 55.6% of the 10-mg atogepant group, 58.7% of the 30-mg group, and 60.8% of the 60-mg group. Approximately 29% patients who received placebo achieved this outcome.
The data indicated that atogepant has a favorable safety profile. The most common adverse events associated with treatment were constipation, nausea, and upper respiratory tract infection.
Dr. Rapoport, who is also a clinical professor of neurology at UCLA, noted that he was impressed with the efficacy.
“I’m not as impressed with the adverse events, but they’re not serious, and they don’t necessarily last,” he said.
Although being able to prescribe a single drug for acute and preventive treatment may be an advantage, it remains to be seen whether the tolerability and price of atogepant will be barriers for patients, Dr. Rapoport added.
How the approval will affect clinical practice is also unclear, he noted.
“If you’re going to start someone on a preventive, especially if it’s a woman of childbearing potential, you might just consider one of the two gepants. Doctors will decide once they see how they work,” said Dr. Rapoport.
Not a ‘breakthrough’ treatment
Also commenting ahead of the approval, Elizabeth W. Loder, MD, vice chair for academic affairs in the department of neurology at Brigham and Women’s Hospital, Boston, noted that the “safety of these CGRP medications in pregnancy is uncertain, and there are theoretical reasons to be concerned about it.”
Unlike injectable CGRP medications, atogepant is eliminated from the body relatively quickly after the patient stops taking it, said Dr. Loder, who is also professor of neurology at Harvard Medical School, Boston. However, atogepant may not otherwise differ greatly from other medications of its type.
“I don’t see a reason to think that one of these oral CGRP medicines is much more effective than another one,” said Dr. Loder.
“In my mind, as a clinician who will be prescribing these for patients, it will be cost and the ease of getting it covered that makes the difference,” she added.
These questions may raise concerns. “Those of us who treat patients who do not have private insurance find it very difficult to get these medications for them, even in situations where they have exhausted other alternatives,” said Dr. Loder.
Patients insured by Medicare or Medicaid “usually have no avenue to get some of these new, expensive treatments,” she said.
The approval of atogepant for acute and preventive treatment shows that the distinction between these indications may be artificial, Dr. Loder noted. The approval “will, I hope, help people think more flexibly about the way in which we use medications.”
It is a positive that atogepant has emerged as another option for preventive therapy, but the treatment cannot be considered a breakthrough, Dr. Loder added. The efficacy of atogepant, like that of other preventive treatments for migraine, is modest.
“It would be so nice if we could find things that were more effective than the treatments we currently have,” said Dr. Loder.
A version of this article first appeared on Medscape.com.
Assessing headache severity via migraine symptoms can help predict outcomes
according to an analysis of data from thousands of headache sufferers who recorded variables like pain and duration in a daily digital diary.
“Our hope is that this work serves as foundational basis for better understanding the complexity of headache as a symptom-based condition,” James S. McGinley, PhD, of Vector Psychometric Group in Chapel Hill, N.C., and coauthors wrote. The study was published in Cephalalgia.
To evaluate whether keeping track of daily headache features can produce a useful, predictive score, the researchers reviewed data from migraine patients that were collected via N1‑Headache, a commercial digital health platform. Ultimately, information from 4,380 adults with a self-reported migraine diagnosis was analyzed; the sample was 90% female and their mean age was 37 years. Study participants reported an average of 33 headaches per month over the last 3 months. Nine patient-reported variables were initially considered in calculating the Headache Day Severity (HDS) score: pain intensity, headache duration, aura, pulsating/throbbing pain, unilateral pain, pain aggravation by activity, nausea/vomiting, photophobia, and phonophobia.
After determining that unilateral pain was not a meaningful variable, the researchers’ model found that, for every 1 standard deviation increase in HDS, the patient’s odds of physician visit increased by 71% (odds ratio, 1.71; 95% confidence interval, 1.32-2.21) and the odds of an ED visit increased by 342% (OR, 4.42; 95% CI, 2.23-7.60). They also found that the likelihood of missed work or school increased by 190% (OR, 2.90; 95% CI, 2.56-3.29), the chances of missing household work increased by 237% (OR, 3.37; 95% CI, 3.06-3.72) and the odds of missing other leisure or social activity increased by 228% (OR, 3.28; 95% CI, 2.97-3.64).
Tracking multiple variables
“We encourage all of our patients to monitor their headaches; there are just too many variables to try to keep it in your head,” Robert Cowan, MD, professor of neurology and chief of the division of headache medicine at Stanford (Calif.) University, said in an interview. He referenced a previous study from the University of Washington where patients were asked to track their headaches; that data was then compared against their self-reported headaches at a quarterly physician visit.
“What they found was there was absolutely no correlation with reported frequency of headache at the visit and what was seen in the tracker,” he said. “If patients had a headache in the previous 3 days before their visit, they felt that their headaches were poorly controlled. If they hadn’t, they thought their headaches were under good control. So the value of tracking is pretty clear.”
He added that, while not every headache sufferer needs to track their daily routines and symptoms, once those symptoms interfere with your life on a day-to-day basis, it’s probably time to consider keeping tabs on yourself with a tool of some sort. And while this study’s calculated HDS score supports the idea of migraine’s complexity, it also leaves unanswered the question of how to treat patients with severe symptoms.
“Frequently,” he said, “we’ll see patients who say: ‘I can deal with the pain, but the nausea makes it impossible to work, or the light sensitivity makes it impossible to go outside.’ The big question within the headache community is, can you treat migraine and have it address the whole spectrum, from dizziness to light sensitivity to sound sensitivity to vertigo, or should you be going after individual symptoms? That’s a controversy that rages on; I think most of us go for a combination. We’re in a polypharmacy phase: ‘If nausea is a big problem, take this, but we also try to prevent the whole migraine complex, so take this as well.’ ”
The authors acknowledged their study’s limitations, including the inability to determine how many participants’ migraines were formally diagnosed by a trained medical professional and the lack of generalizability of data from a convenience sample, though they added that patients who independently track their own headaches “may be representative of those who would participate in a clinical trial.” In addition, as seven of the nine features were collected in N1‑Headache on a yes/no scale, they recognized that “increasing the number of response options for each item may improve our ability to measure HDS.”
The study was funded by Amgen through the Competitive Grant Program in Migraine Research. The authors declared several potential conflicts of interest, including receiving funding, research support, salary, and honoraria from various pharmaceutical companies.
according to an analysis of data from thousands of headache sufferers who recorded variables like pain and duration in a daily digital diary.
“Our hope is that this work serves as foundational basis for better understanding the complexity of headache as a symptom-based condition,” James S. McGinley, PhD, of Vector Psychometric Group in Chapel Hill, N.C., and coauthors wrote. The study was published in Cephalalgia.
To evaluate whether keeping track of daily headache features can produce a useful, predictive score, the researchers reviewed data from migraine patients that were collected via N1‑Headache, a commercial digital health platform. Ultimately, information from 4,380 adults with a self-reported migraine diagnosis was analyzed; the sample was 90% female and their mean age was 37 years. Study participants reported an average of 33 headaches per month over the last 3 months. Nine patient-reported variables were initially considered in calculating the Headache Day Severity (HDS) score: pain intensity, headache duration, aura, pulsating/throbbing pain, unilateral pain, pain aggravation by activity, nausea/vomiting, photophobia, and phonophobia.
After determining that unilateral pain was not a meaningful variable, the researchers’ model found that, for every 1 standard deviation increase in HDS, the patient’s odds of physician visit increased by 71% (odds ratio, 1.71; 95% confidence interval, 1.32-2.21) and the odds of an ED visit increased by 342% (OR, 4.42; 95% CI, 2.23-7.60). They also found that the likelihood of missed work or school increased by 190% (OR, 2.90; 95% CI, 2.56-3.29), the chances of missing household work increased by 237% (OR, 3.37; 95% CI, 3.06-3.72) and the odds of missing other leisure or social activity increased by 228% (OR, 3.28; 95% CI, 2.97-3.64).
Tracking multiple variables
“We encourage all of our patients to monitor their headaches; there are just too many variables to try to keep it in your head,” Robert Cowan, MD, professor of neurology and chief of the division of headache medicine at Stanford (Calif.) University, said in an interview. He referenced a previous study from the University of Washington where patients were asked to track their headaches; that data was then compared against their self-reported headaches at a quarterly physician visit.
“What they found was there was absolutely no correlation with reported frequency of headache at the visit and what was seen in the tracker,” he said. “If patients had a headache in the previous 3 days before their visit, they felt that their headaches were poorly controlled. If they hadn’t, they thought their headaches were under good control. So the value of tracking is pretty clear.”
He added that, while not every headache sufferer needs to track their daily routines and symptoms, once those symptoms interfere with your life on a day-to-day basis, it’s probably time to consider keeping tabs on yourself with a tool of some sort. And while this study’s calculated HDS score supports the idea of migraine’s complexity, it also leaves unanswered the question of how to treat patients with severe symptoms.
“Frequently,” he said, “we’ll see patients who say: ‘I can deal with the pain, but the nausea makes it impossible to work, or the light sensitivity makes it impossible to go outside.’ The big question within the headache community is, can you treat migraine and have it address the whole spectrum, from dizziness to light sensitivity to sound sensitivity to vertigo, or should you be going after individual symptoms? That’s a controversy that rages on; I think most of us go for a combination. We’re in a polypharmacy phase: ‘If nausea is a big problem, take this, but we also try to prevent the whole migraine complex, so take this as well.’ ”
The authors acknowledged their study’s limitations, including the inability to determine how many participants’ migraines were formally diagnosed by a trained medical professional and the lack of generalizability of data from a convenience sample, though they added that patients who independently track their own headaches “may be representative of those who would participate in a clinical trial.” In addition, as seven of the nine features were collected in N1‑Headache on a yes/no scale, they recognized that “increasing the number of response options for each item may improve our ability to measure HDS.”
The study was funded by Amgen through the Competitive Grant Program in Migraine Research. The authors declared several potential conflicts of interest, including receiving funding, research support, salary, and honoraria from various pharmaceutical companies.
according to an analysis of data from thousands of headache sufferers who recorded variables like pain and duration in a daily digital diary.
“Our hope is that this work serves as foundational basis for better understanding the complexity of headache as a symptom-based condition,” James S. McGinley, PhD, of Vector Psychometric Group in Chapel Hill, N.C., and coauthors wrote. The study was published in Cephalalgia.
To evaluate whether keeping track of daily headache features can produce a useful, predictive score, the researchers reviewed data from migraine patients that were collected via N1‑Headache, a commercial digital health platform. Ultimately, information from 4,380 adults with a self-reported migraine diagnosis was analyzed; the sample was 90% female and their mean age was 37 years. Study participants reported an average of 33 headaches per month over the last 3 months. Nine patient-reported variables were initially considered in calculating the Headache Day Severity (HDS) score: pain intensity, headache duration, aura, pulsating/throbbing pain, unilateral pain, pain aggravation by activity, nausea/vomiting, photophobia, and phonophobia.
After determining that unilateral pain was not a meaningful variable, the researchers’ model found that, for every 1 standard deviation increase in HDS, the patient’s odds of physician visit increased by 71% (odds ratio, 1.71; 95% confidence interval, 1.32-2.21) and the odds of an ED visit increased by 342% (OR, 4.42; 95% CI, 2.23-7.60). They also found that the likelihood of missed work or school increased by 190% (OR, 2.90; 95% CI, 2.56-3.29), the chances of missing household work increased by 237% (OR, 3.37; 95% CI, 3.06-3.72) and the odds of missing other leisure or social activity increased by 228% (OR, 3.28; 95% CI, 2.97-3.64).
Tracking multiple variables
“We encourage all of our patients to monitor their headaches; there are just too many variables to try to keep it in your head,” Robert Cowan, MD, professor of neurology and chief of the division of headache medicine at Stanford (Calif.) University, said in an interview. He referenced a previous study from the University of Washington where patients were asked to track their headaches; that data was then compared against their self-reported headaches at a quarterly physician visit.
“What they found was there was absolutely no correlation with reported frequency of headache at the visit and what was seen in the tracker,” he said. “If patients had a headache in the previous 3 days before their visit, they felt that their headaches were poorly controlled. If they hadn’t, they thought their headaches were under good control. So the value of tracking is pretty clear.”
He added that, while not every headache sufferer needs to track their daily routines and symptoms, once those symptoms interfere with your life on a day-to-day basis, it’s probably time to consider keeping tabs on yourself with a tool of some sort. And while this study’s calculated HDS score supports the idea of migraine’s complexity, it also leaves unanswered the question of how to treat patients with severe symptoms.
“Frequently,” he said, “we’ll see patients who say: ‘I can deal with the pain, but the nausea makes it impossible to work, or the light sensitivity makes it impossible to go outside.’ The big question within the headache community is, can you treat migraine and have it address the whole spectrum, from dizziness to light sensitivity to sound sensitivity to vertigo, or should you be going after individual symptoms? That’s a controversy that rages on; I think most of us go for a combination. We’re in a polypharmacy phase: ‘If nausea is a big problem, take this, but we also try to prevent the whole migraine complex, so take this as well.’ ”
The authors acknowledged their study’s limitations, including the inability to determine how many participants’ migraines were formally diagnosed by a trained medical professional and the lack of generalizability of data from a convenience sample, though they added that patients who independently track their own headaches “may be representative of those who would participate in a clinical trial.” In addition, as seven of the nine features were collected in N1‑Headache on a yes/no scale, they recognized that “increasing the number of response options for each item may improve our ability to measure HDS.”
The study was funded by Amgen through the Competitive Grant Program in Migraine Research. The authors declared several potential conflicts of interest, including receiving funding, research support, salary, and honoraria from various pharmaceutical companies.
FROM CEPHALALGIA
Atogepant reduces migraine days: ADVANCE trial results published
full results from a phase 3 trial suggest.
AbbVie, the company developing the oral therapy, announced topline results of the ADVANCE trial of atogepant last year. Safety results were presented in April at the 2021 annual meeting of the American Academy of Neurology.
The full results were published online Aug. 19 in the New England Journal of Medicine ahead of the upcoming target action date of the U.S. Food and Drug Administration.
The multicenter study included nearly 900 patients who were randomly assigned to receive either placebo or one of three doses of atogepant for 12 weeks. The mean number of monthly migraine days decreased by about 4 for all three doses of the active treatment, compared with a reduction of 2.5 days with placebo.
“Overall, this study showed us that atogepant was safe and surprisingly seems to be pretty effective regardless of the dose,” said lead author Jessica Ailani, MD, director of MedStar Georgetown Headache Center and associate professor of neurology at Georgetown University, Washington.
All doses effective
The study included 873 patients with episodic migraine with or without aura. Patients who were not assigned to the placebo control group received either 10 mg, 30 mg, or 60 mg of atogepant once daily.
After a 4-week screening period, all patients received treatment for 12 weeks and then entered a 4-week safety follow-up period. In total, the participants completed eight scheduled clinical visits.
The mean reduction from baseline in the mean number of migraine days per month was 3.7 with the 10-mg dose of atogepant, 3.9 with the 30-mg dose, 4.2 with the 60-mg dose, and 2.5 with placebo. The differences between each active dose and placebo was statistically significant (P < .001).
Treatment with the CGRP inhibitor was also associated with a reduction in the mean number of headache days per month. The mean reduction from baseline was 3.9 days for the 10-mg dose, 4.0 days for the 30-mg dose, 4.2 days for the 60-mg dose, and 2.5 days for placebo (P < .001 for all comparisons with placebo).
In addition, for 55.6% of the 10-mg group, 58.7% of the 30-mg group, 60.8% of the 60-mg group, and 29.0% of the control group, there was a reduction of at least 50% in the 3-month average number of migraine days per month (P < .001 for each vs. placebo).
The most commonly reported adverse events (AEs) among patients who received atogepant were constipation (6.9%-7.7% across doses), nausea (4.4%-6.1%), and upper respiratory tract infection (1.4%-3.9%). Frequency of AEs did not differ between the active-treatment groups and the control group, and no relationships between AEs and atogepant dose were observed.
Multidose flexibility
“Side effects were pretty even across the board,” said Dr. Ailani. She noted that the reported AEs were expected because of atogepant’s mechanism of action. In addition, the rate of discontinuation in the study was low.
The proportion of participants who experienced a reduction in monthly migraine days of at least 50% grew as time passed. “By the end of this study, your chance of having a greater than 50% response is about 75%,” Dr. Ailani said.
“Imagine telling your patient, ‘You stick on this drug for 3 months, and I can almost guarantee you that you’re going to get better,’” she added.
Although the treatment has no drug-drug contraindications, drug-drug interactions may occur. “The availability of various doses would allow clinicians to adjust treatment to avoid potential drug-drug interactions,” said Dr. Ailani. “That multidose flexibility is very important.”
An FDA decision on atogepant could be made in the coming months. “I’m hopeful, as a clinician, that it is positive news, because we really have waited a long time for something like this,” Dr. Ailani said.
“You can easily identify patients who would do well on this medication,” she added.
In a different study of atogepant among patients with chronic migraine, there were recruitment delays because of the pandemic. That study is now almost complete, Dr. Ailani reported.
“Well-conducted study”
Commenting on the findings, Kathleen B. Digre, MD, chief of the division of headache and neuro-ophthalmology at the University of Utah Health, Salt Lake City, expressed enthusiasm for the experimental drug. “I’m excited to see another treatment modality for migraine,” said Dr. Digre, who was not involved with the research. “It was a very well-conducted study,” she added.
The treatment arms were almost identical in regard to disease severity, and all the doses showed an effect. Although the difference in reduction of monthly migraine days in comparison with placebo was numerically small, “for people who have frequent migraine, it’s important,” Dr. Digre said.
The results for atogepant should be viewed in a larger context, however. “Even though it’s a treatment that works better than placebo for well-matched controls, it may not be a medication that everybody’s going to respond to,” she noted. “And we can’t generalize it for some of the most disabled people, which is for chronic migraine,” she said.
It is significant that the study was published in the New England Journal of Medicine, Dr. Digre noted. “Sometimes migraine is dismissed as not important and not affecting people’s lives,” she said. “That makes me very happy to see migraine being taken seriously by our major journals.”
In addition, she noted that the prospects for FDA approval of atogepant seem favorable. “I’m hopeful that they will approve it, because it’s got a low side-effect profile, plus it’s effective.”
Migraine-specific preventive therapy has emerged only in the past few years. “I’m so excited to see this surge of preventive medicine for migraine,” Dr. Digre said. “It’s so important, because we see so many people who are disabled by migraine,” she added.
The study was funded by Allergan before atogepant was acquired by AbbVie. Dr. Ailani has received honoraria from AbbVie for consulting, has received compensation from Allergan and AbbVie for participating in a speakers’ bureau, and has received clinical trial grants from Allergan. Dr. Digre has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
full results from a phase 3 trial suggest.
AbbVie, the company developing the oral therapy, announced topline results of the ADVANCE trial of atogepant last year. Safety results were presented in April at the 2021 annual meeting of the American Academy of Neurology.
The full results were published online Aug. 19 in the New England Journal of Medicine ahead of the upcoming target action date of the U.S. Food and Drug Administration.
The multicenter study included nearly 900 patients who were randomly assigned to receive either placebo or one of three doses of atogepant for 12 weeks. The mean number of monthly migraine days decreased by about 4 for all three doses of the active treatment, compared with a reduction of 2.5 days with placebo.
“Overall, this study showed us that atogepant was safe and surprisingly seems to be pretty effective regardless of the dose,” said lead author Jessica Ailani, MD, director of MedStar Georgetown Headache Center and associate professor of neurology at Georgetown University, Washington.
All doses effective
The study included 873 patients with episodic migraine with or without aura. Patients who were not assigned to the placebo control group received either 10 mg, 30 mg, or 60 mg of atogepant once daily.
After a 4-week screening period, all patients received treatment for 12 weeks and then entered a 4-week safety follow-up period. In total, the participants completed eight scheduled clinical visits.
The mean reduction from baseline in the mean number of migraine days per month was 3.7 with the 10-mg dose of atogepant, 3.9 with the 30-mg dose, 4.2 with the 60-mg dose, and 2.5 with placebo. The differences between each active dose and placebo was statistically significant (P < .001).
Treatment with the CGRP inhibitor was also associated with a reduction in the mean number of headache days per month. The mean reduction from baseline was 3.9 days for the 10-mg dose, 4.0 days for the 30-mg dose, 4.2 days for the 60-mg dose, and 2.5 days for placebo (P < .001 for all comparisons with placebo).
In addition, for 55.6% of the 10-mg group, 58.7% of the 30-mg group, 60.8% of the 60-mg group, and 29.0% of the control group, there was a reduction of at least 50% in the 3-month average number of migraine days per month (P < .001 for each vs. placebo).
The most commonly reported adverse events (AEs) among patients who received atogepant were constipation (6.9%-7.7% across doses), nausea (4.4%-6.1%), and upper respiratory tract infection (1.4%-3.9%). Frequency of AEs did not differ between the active-treatment groups and the control group, and no relationships between AEs and atogepant dose were observed.
Multidose flexibility
“Side effects were pretty even across the board,” said Dr. Ailani. She noted that the reported AEs were expected because of atogepant’s mechanism of action. In addition, the rate of discontinuation in the study was low.
The proportion of participants who experienced a reduction in monthly migraine days of at least 50% grew as time passed. “By the end of this study, your chance of having a greater than 50% response is about 75%,” Dr. Ailani said.
“Imagine telling your patient, ‘You stick on this drug for 3 months, and I can almost guarantee you that you’re going to get better,’” she added.
Although the treatment has no drug-drug contraindications, drug-drug interactions may occur. “The availability of various doses would allow clinicians to adjust treatment to avoid potential drug-drug interactions,” said Dr. Ailani. “That multidose flexibility is very important.”
An FDA decision on atogepant could be made in the coming months. “I’m hopeful, as a clinician, that it is positive news, because we really have waited a long time for something like this,” Dr. Ailani said.
“You can easily identify patients who would do well on this medication,” she added.
In a different study of atogepant among patients with chronic migraine, there were recruitment delays because of the pandemic. That study is now almost complete, Dr. Ailani reported.
“Well-conducted study”
Commenting on the findings, Kathleen B. Digre, MD, chief of the division of headache and neuro-ophthalmology at the University of Utah Health, Salt Lake City, expressed enthusiasm for the experimental drug. “I’m excited to see another treatment modality for migraine,” said Dr. Digre, who was not involved with the research. “It was a very well-conducted study,” she added.
The treatment arms were almost identical in regard to disease severity, and all the doses showed an effect. Although the difference in reduction of monthly migraine days in comparison with placebo was numerically small, “for people who have frequent migraine, it’s important,” Dr. Digre said.
The results for atogepant should be viewed in a larger context, however. “Even though it’s a treatment that works better than placebo for well-matched controls, it may not be a medication that everybody’s going to respond to,” she noted. “And we can’t generalize it for some of the most disabled people, which is for chronic migraine,” she said.
It is significant that the study was published in the New England Journal of Medicine, Dr. Digre noted. “Sometimes migraine is dismissed as not important and not affecting people’s lives,” she said. “That makes me very happy to see migraine being taken seriously by our major journals.”
In addition, she noted that the prospects for FDA approval of atogepant seem favorable. “I’m hopeful that they will approve it, because it’s got a low side-effect profile, plus it’s effective.”
Migraine-specific preventive therapy has emerged only in the past few years. “I’m so excited to see this surge of preventive medicine for migraine,” Dr. Digre said. “It’s so important, because we see so many people who are disabled by migraine,” she added.
The study was funded by Allergan before atogepant was acquired by AbbVie. Dr. Ailani has received honoraria from AbbVie for consulting, has received compensation from Allergan and AbbVie for participating in a speakers’ bureau, and has received clinical trial grants from Allergan. Dr. Digre has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
full results from a phase 3 trial suggest.
AbbVie, the company developing the oral therapy, announced topline results of the ADVANCE trial of atogepant last year. Safety results were presented in April at the 2021 annual meeting of the American Academy of Neurology.
The full results were published online Aug. 19 in the New England Journal of Medicine ahead of the upcoming target action date of the U.S. Food and Drug Administration.
The multicenter study included nearly 900 patients who were randomly assigned to receive either placebo or one of three doses of atogepant for 12 weeks. The mean number of monthly migraine days decreased by about 4 for all three doses of the active treatment, compared with a reduction of 2.5 days with placebo.
“Overall, this study showed us that atogepant was safe and surprisingly seems to be pretty effective regardless of the dose,” said lead author Jessica Ailani, MD, director of MedStar Georgetown Headache Center and associate professor of neurology at Georgetown University, Washington.
All doses effective
The study included 873 patients with episodic migraine with or without aura. Patients who were not assigned to the placebo control group received either 10 mg, 30 mg, or 60 mg of atogepant once daily.
After a 4-week screening period, all patients received treatment for 12 weeks and then entered a 4-week safety follow-up period. In total, the participants completed eight scheduled clinical visits.
The mean reduction from baseline in the mean number of migraine days per month was 3.7 with the 10-mg dose of atogepant, 3.9 with the 30-mg dose, 4.2 with the 60-mg dose, and 2.5 with placebo. The differences between each active dose and placebo was statistically significant (P < .001).
Treatment with the CGRP inhibitor was also associated with a reduction in the mean number of headache days per month. The mean reduction from baseline was 3.9 days for the 10-mg dose, 4.0 days for the 30-mg dose, 4.2 days for the 60-mg dose, and 2.5 days for placebo (P < .001 for all comparisons with placebo).
In addition, for 55.6% of the 10-mg group, 58.7% of the 30-mg group, 60.8% of the 60-mg group, and 29.0% of the control group, there was a reduction of at least 50% in the 3-month average number of migraine days per month (P < .001 for each vs. placebo).
The most commonly reported adverse events (AEs) among patients who received atogepant were constipation (6.9%-7.7% across doses), nausea (4.4%-6.1%), and upper respiratory tract infection (1.4%-3.9%). Frequency of AEs did not differ between the active-treatment groups and the control group, and no relationships between AEs and atogepant dose were observed.
Multidose flexibility
“Side effects were pretty even across the board,” said Dr. Ailani. She noted that the reported AEs were expected because of atogepant’s mechanism of action. In addition, the rate of discontinuation in the study was low.
The proportion of participants who experienced a reduction in monthly migraine days of at least 50% grew as time passed. “By the end of this study, your chance of having a greater than 50% response is about 75%,” Dr. Ailani said.
“Imagine telling your patient, ‘You stick on this drug for 3 months, and I can almost guarantee you that you’re going to get better,’” she added.
Although the treatment has no drug-drug contraindications, drug-drug interactions may occur. “The availability of various doses would allow clinicians to adjust treatment to avoid potential drug-drug interactions,” said Dr. Ailani. “That multidose flexibility is very important.”
An FDA decision on atogepant could be made in the coming months. “I’m hopeful, as a clinician, that it is positive news, because we really have waited a long time for something like this,” Dr. Ailani said.
“You can easily identify patients who would do well on this medication,” she added.
In a different study of atogepant among patients with chronic migraine, there were recruitment delays because of the pandemic. That study is now almost complete, Dr. Ailani reported.
“Well-conducted study”
Commenting on the findings, Kathleen B. Digre, MD, chief of the division of headache and neuro-ophthalmology at the University of Utah Health, Salt Lake City, expressed enthusiasm for the experimental drug. “I’m excited to see another treatment modality for migraine,” said Dr. Digre, who was not involved with the research. “It was a very well-conducted study,” she added.
The treatment arms were almost identical in regard to disease severity, and all the doses showed an effect. Although the difference in reduction of monthly migraine days in comparison with placebo was numerically small, “for people who have frequent migraine, it’s important,” Dr. Digre said.
The results for atogepant should be viewed in a larger context, however. “Even though it’s a treatment that works better than placebo for well-matched controls, it may not be a medication that everybody’s going to respond to,” she noted. “And we can’t generalize it for some of the most disabled people, which is for chronic migraine,” she said.
It is significant that the study was published in the New England Journal of Medicine, Dr. Digre noted. “Sometimes migraine is dismissed as not important and not affecting people’s lives,” she said. “That makes me very happy to see migraine being taken seriously by our major journals.”
In addition, she noted that the prospects for FDA approval of atogepant seem favorable. “I’m hopeful that they will approve it, because it’s got a low side-effect profile, plus it’s effective.”
Migraine-specific preventive therapy has emerged only in the past few years. “I’m so excited to see this surge of preventive medicine for migraine,” Dr. Digre said. “It’s so important, because we see so many people who are disabled by migraine,” she added.
The study was funded by Allergan before atogepant was acquired by AbbVie. Dr. Ailani has received honoraria from AbbVie for consulting, has received compensation from Allergan and AbbVie for participating in a speakers’ bureau, and has received clinical trial grants from Allergan. Dr. Digre has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Headache seen affecting some pregnancy outcomes
, according to results from an observational study.
Migraine during pregnancy has been associated in previous studies with hypertensive pregnancy complications including preeclampsia; however, little is known about other headache types and their effects on pregnancy and birth outcomes.
For their research, published online July 20 in Cephalalgia, Isabella Neri, MD, PhD, and colleagues at Hospital Policlinico of Modena, Italy, looked at headache status for 515 consecutive pregnant women evaluated during their first trimester and followed through childbirth.
Altogether 224 women, or 43.5% of the cohort, were diagnosed with migraine without aura (n = 72), migraine with aura (n = 27), or tension-type headache (n = 125). The authors did not report on the severity or frequency of headaches.
Women with migraine with aura and tension-type headache saw higher rates of small-for-gestational-age infants (25.9% and 10.4% of births, respectively) compared with 5.5% for women without headache. Women presenting with tension-type headache saw elevated risk for small-for-gestational-age infants (odds ratio [OR] 4.19, P = .004) as did women with migraine with aura (OR 5.37, P = .02).
Admission to neonatal intensive care was significantly higher in all the headache groups. However, the authors found no statistically significant associations between headaches and any other perinatal outcome investigated in the study, including gestational diabetes, placental abruption, gestational hypertension, and preterm delivery.
A previous study conducted by the same research group had reported a relationship between migraine and gestational hypertension. The authors cited the small sample size of the migraine groups in the current study, “the diverse features of the population,” and the popularity of low-dose aspirin administration as potentially affecting that outcome.
Interpret findings with caution
Asked by this news organization to comment on the research, two headache neurologists praised Dr. Neri and colleagues’ research for focusing on an understudied topic – but also said that the results would not change their practice unless replicated in larger studies.
Elizabeth W. Loder, MD, MPH, chief emeritus of the division of headache at Brigham and Women’s Faulkner Hospital in Boston, urged caution in interpreting the findings, particularly with regard to tension-type headache. “This study adds to information suggesting that pregnancy complications probably are higher in women who have migraine with aura, and there’s biological plausibility for that,” Dr. Loder said. “Having aura means you may have some vascular abnormalities and things that logically might be associated with an increased risk of small-for-gestational age infants.” But the small size of the migraine-with-aura group in this study – 27 women – and the fact that other perinatal outcomes measured in the study did not reach significance, allows for the possibility that the small-for-gestational-age findings were due to chance, Dr. Loder noted.
With tension-type headache, a biological rationale for small-for-gestational-age risk is more elusive, Dr. Loder said. “I would want to see that association replicated in another study before I thought that I needed to warn women with tension-type headache about this potential outcome. There’s lot of uncertainty here about the magnitude of the risk.”
While Dr. Neri and colleagues described the instruments used in their study to diagnose migraine and migraine with aura, they did not explain how tension-type headache was diagnosed.
Tension-type headache, while common, is still not well characterized, Dr. Loder noted, and may represent a heterogeneous condition or the milder end of a biological continuum that includes migraine with aura. Also, the group in the study had a higher prevalence of smoking, and though the authors made statistical adjustments for smoking status, “smokers are systematically different than people who aren’t in other ways that could be associated with these outcomes,” Dr. Loder said.
While the authors of the study suggested that interventions might be indicated for women with tension-type headache in pregnancy, “showing an association doesn’t necessarily mean that intervening would make a difference” on pregnancy outcomes, Dr. Loder said.
Amaal J. Starling, MD, of the Mayo Clinic in Phoenix, Ariz., said in an interview that she, too, appreciated that this study looked at pregnancy outcomes in the setting of headache disorders. “Unfortunately even though headache disorders and especially migraine affect women so much, we still know very little about migraine in pregnancy,” she said.
Dr. Starling noted that many women with migraine are discouraged by their health care providers from becoming pregnant, because of the false belief that migraine cannot be managed in pregnancy. In her own practice, she said, she treats many patients with severe headache who become pregnant and who require pharmacological intervention during pregnancy.
This does not mean she regards headache in pregnancy as innocent. “I want patients to be on high alert for changes in headache symptoms in pregnancy. If someone has worsening of headache or migraine or aura in the setting of pregnancy, we consider that a red flag,” potentially indicating complications such as high blood pressure, gestational hypertension, or a blood clot.
Like Dr. Loder, Dr. Starling said she was not surprised by Dr. Neri and colleagues’ finding that migraine with aura might impact pregnancy outcomes. “We know that migraine with aura has a lot of vascular abnormalities that underlie the pathogenesis,” she said.
Dr. Starling found the findings related to tension-type headache less convincing, not least because the diagnostic criteria for tension-type headache was not made clear in the study. “I view this as an exploratory study that says maybe there’s a signal here. A larger epidemiological study would need to be done to confirm or refute this data,” Dr. Starling said. Until the findings can be replicated, “this study would not affect my clinical practice in any way.”
Dr. Neri and colleagues described no outside funding for their research or financial conflicts of interest. Dr. Starling has received consulting fees from pharmaceutical manufacturers but reported no disclosures relevant to the study discussed. Dr. Loder reported no financial conflicts of interest.
, according to results from an observational study.
Migraine during pregnancy has been associated in previous studies with hypertensive pregnancy complications including preeclampsia; however, little is known about other headache types and their effects on pregnancy and birth outcomes.
For their research, published online July 20 in Cephalalgia, Isabella Neri, MD, PhD, and colleagues at Hospital Policlinico of Modena, Italy, looked at headache status for 515 consecutive pregnant women evaluated during their first trimester and followed through childbirth.
Altogether 224 women, or 43.5% of the cohort, were diagnosed with migraine without aura (n = 72), migraine with aura (n = 27), or tension-type headache (n = 125). The authors did not report on the severity or frequency of headaches.
Women with migraine with aura and tension-type headache saw higher rates of small-for-gestational-age infants (25.9% and 10.4% of births, respectively) compared with 5.5% for women without headache. Women presenting with tension-type headache saw elevated risk for small-for-gestational-age infants (odds ratio [OR] 4.19, P = .004) as did women with migraine with aura (OR 5.37, P = .02).
Admission to neonatal intensive care was significantly higher in all the headache groups. However, the authors found no statistically significant associations between headaches and any other perinatal outcome investigated in the study, including gestational diabetes, placental abruption, gestational hypertension, and preterm delivery.
A previous study conducted by the same research group had reported a relationship between migraine and gestational hypertension. The authors cited the small sample size of the migraine groups in the current study, “the diverse features of the population,” and the popularity of low-dose aspirin administration as potentially affecting that outcome.
Interpret findings with caution
Asked by this news organization to comment on the research, two headache neurologists praised Dr. Neri and colleagues’ research for focusing on an understudied topic – but also said that the results would not change their practice unless replicated in larger studies.
Elizabeth W. Loder, MD, MPH, chief emeritus of the division of headache at Brigham and Women’s Faulkner Hospital in Boston, urged caution in interpreting the findings, particularly with regard to tension-type headache. “This study adds to information suggesting that pregnancy complications probably are higher in women who have migraine with aura, and there’s biological plausibility for that,” Dr. Loder said. “Having aura means you may have some vascular abnormalities and things that logically might be associated with an increased risk of small-for-gestational age infants.” But the small size of the migraine-with-aura group in this study – 27 women – and the fact that other perinatal outcomes measured in the study did not reach significance, allows for the possibility that the small-for-gestational-age findings were due to chance, Dr. Loder noted.
With tension-type headache, a biological rationale for small-for-gestational-age risk is more elusive, Dr. Loder said. “I would want to see that association replicated in another study before I thought that I needed to warn women with tension-type headache about this potential outcome. There’s lot of uncertainty here about the magnitude of the risk.”
While Dr. Neri and colleagues described the instruments used in their study to diagnose migraine and migraine with aura, they did not explain how tension-type headache was diagnosed.
Tension-type headache, while common, is still not well characterized, Dr. Loder noted, and may represent a heterogeneous condition or the milder end of a biological continuum that includes migraine with aura. Also, the group in the study had a higher prevalence of smoking, and though the authors made statistical adjustments for smoking status, “smokers are systematically different than people who aren’t in other ways that could be associated with these outcomes,” Dr. Loder said.
While the authors of the study suggested that interventions might be indicated for women with tension-type headache in pregnancy, “showing an association doesn’t necessarily mean that intervening would make a difference” on pregnancy outcomes, Dr. Loder said.
Amaal J. Starling, MD, of the Mayo Clinic in Phoenix, Ariz., said in an interview that she, too, appreciated that this study looked at pregnancy outcomes in the setting of headache disorders. “Unfortunately even though headache disorders and especially migraine affect women so much, we still know very little about migraine in pregnancy,” she said.
Dr. Starling noted that many women with migraine are discouraged by their health care providers from becoming pregnant, because of the false belief that migraine cannot be managed in pregnancy. In her own practice, she said, she treats many patients with severe headache who become pregnant and who require pharmacological intervention during pregnancy.
This does not mean she regards headache in pregnancy as innocent. “I want patients to be on high alert for changes in headache symptoms in pregnancy. If someone has worsening of headache or migraine or aura in the setting of pregnancy, we consider that a red flag,” potentially indicating complications such as high blood pressure, gestational hypertension, or a blood clot.
Like Dr. Loder, Dr. Starling said she was not surprised by Dr. Neri and colleagues’ finding that migraine with aura might impact pregnancy outcomes. “We know that migraine with aura has a lot of vascular abnormalities that underlie the pathogenesis,” she said.
Dr. Starling found the findings related to tension-type headache less convincing, not least because the diagnostic criteria for tension-type headache was not made clear in the study. “I view this as an exploratory study that says maybe there’s a signal here. A larger epidemiological study would need to be done to confirm or refute this data,” Dr. Starling said. Until the findings can be replicated, “this study would not affect my clinical practice in any way.”
Dr. Neri and colleagues described no outside funding for their research or financial conflicts of interest. Dr. Starling has received consulting fees from pharmaceutical manufacturers but reported no disclosures relevant to the study discussed. Dr. Loder reported no financial conflicts of interest.
, according to results from an observational study.
Migraine during pregnancy has been associated in previous studies with hypertensive pregnancy complications including preeclampsia; however, little is known about other headache types and their effects on pregnancy and birth outcomes.
For their research, published online July 20 in Cephalalgia, Isabella Neri, MD, PhD, and colleagues at Hospital Policlinico of Modena, Italy, looked at headache status for 515 consecutive pregnant women evaluated during their first trimester and followed through childbirth.
Altogether 224 women, or 43.5% of the cohort, were diagnosed with migraine without aura (n = 72), migraine with aura (n = 27), or tension-type headache (n = 125). The authors did not report on the severity or frequency of headaches.
Women with migraine with aura and tension-type headache saw higher rates of small-for-gestational-age infants (25.9% and 10.4% of births, respectively) compared with 5.5% for women without headache. Women presenting with tension-type headache saw elevated risk for small-for-gestational-age infants (odds ratio [OR] 4.19, P = .004) as did women with migraine with aura (OR 5.37, P = .02).
Admission to neonatal intensive care was significantly higher in all the headache groups. However, the authors found no statistically significant associations between headaches and any other perinatal outcome investigated in the study, including gestational diabetes, placental abruption, gestational hypertension, and preterm delivery.
A previous study conducted by the same research group had reported a relationship between migraine and gestational hypertension. The authors cited the small sample size of the migraine groups in the current study, “the diverse features of the population,” and the popularity of low-dose aspirin administration as potentially affecting that outcome.
Interpret findings with caution
Asked by this news organization to comment on the research, two headache neurologists praised Dr. Neri and colleagues’ research for focusing on an understudied topic – but also said that the results would not change their practice unless replicated in larger studies.
Elizabeth W. Loder, MD, MPH, chief emeritus of the division of headache at Brigham and Women’s Faulkner Hospital in Boston, urged caution in interpreting the findings, particularly with regard to tension-type headache. “This study adds to information suggesting that pregnancy complications probably are higher in women who have migraine with aura, and there’s biological plausibility for that,” Dr. Loder said. “Having aura means you may have some vascular abnormalities and things that logically might be associated with an increased risk of small-for-gestational age infants.” But the small size of the migraine-with-aura group in this study – 27 women – and the fact that other perinatal outcomes measured in the study did not reach significance, allows for the possibility that the small-for-gestational-age findings were due to chance, Dr. Loder noted.
With tension-type headache, a biological rationale for small-for-gestational-age risk is more elusive, Dr. Loder said. “I would want to see that association replicated in another study before I thought that I needed to warn women with tension-type headache about this potential outcome. There’s lot of uncertainty here about the magnitude of the risk.”
While Dr. Neri and colleagues described the instruments used in their study to diagnose migraine and migraine with aura, they did not explain how tension-type headache was diagnosed.
Tension-type headache, while common, is still not well characterized, Dr. Loder noted, and may represent a heterogeneous condition or the milder end of a biological continuum that includes migraine with aura. Also, the group in the study had a higher prevalence of smoking, and though the authors made statistical adjustments for smoking status, “smokers are systematically different than people who aren’t in other ways that could be associated with these outcomes,” Dr. Loder said.
While the authors of the study suggested that interventions might be indicated for women with tension-type headache in pregnancy, “showing an association doesn’t necessarily mean that intervening would make a difference” on pregnancy outcomes, Dr. Loder said.
Amaal J. Starling, MD, of the Mayo Clinic in Phoenix, Ariz., said in an interview that she, too, appreciated that this study looked at pregnancy outcomes in the setting of headache disorders. “Unfortunately even though headache disorders and especially migraine affect women so much, we still know very little about migraine in pregnancy,” she said.
Dr. Starling noted that many women with migraine are discouraged by their health care providers from becoming pregnant, because of the false belief that migraine cannot be managed in pregnancy. In her own practice, she said, she treats many patients with severe headache who become pregnant and who require pharmacological intervention during pregnancy.
This does not mean she regards headache in pregnancy as innocent. “I want patients to be on high alert for changes in headache symptoms in pregnancy. If someone has worsening of headache or migraine or aura in the setting of pregnancy, we consider that a red flag,” potentially indicating complications such as high blood pressure, gestational hypertension, or a blood clot.
Like Dr. Loder, Dr. Starling said she was not surprised by Dr. Neri and colleagues’ finding that migraine with aura might impact pregnancy outcomes. “We know that migraine with aura has a lot of vascular abnormalities that underlie the pathogenesis,” she said.
Dr. Starling found the findings related to tension-type headache less convincing, not least because the diagnostic criteria for tension-type headache was not made clear in the study. “I view this as an exploratory study that says maybe there’s a signal here. A larger epidemiological study would need to be done to confirm or refute this data,” Dr. Starling said. Until the findings can be replicated, “this study would not affect my clinical practice in any way.”
Dr. Neri and colleagues described no outside funding for their research or financial conflicts of interest. Dr. Starling has received consulting fees from pharmaceutical manufacturers but reported no disclosures relevant to the study discussed. Dr. Loder reported no financial conflicts of interest.
FROM CEPHALALGIA
Devices for the treatment of migraine
Remote upper arm neuromodulation and combined occipital and trigeminal neuromodulation lead the way as the newest entries to the field, followed by 8 other devices that are now available or are expected to be soon.
The increasing array of prescription medications for the treatment of migraine are welcome additions for patients who suffer from this life-altering condition and the clinicians who treat it; but not all individuals tolerate oral and injectable therapies, and others face the risk of adverse events and medication overuse headache.1 Fortunately, there are a number of devices available to consider, and still others are awaiting approval from the US Food and Drug Administration (FDA).
Two of the most promising devices are remote upper arm neuromodulation (REN) and combined occipital and trigeminal neuromodulation. Here we highlight data from pivotal trials evaluating these 2 treatment options and provide information about other devices worth consideration.
Remote Upper Arm Neuromodulation (REN)
Nerivio was initially authorized by the FDA for the acute treatment of episodic migraine. Available by prescription, the device is administered by the patient at home.2 It stimulates upper arm peripheral nerves, which induces conditioned pain modulation (CPM) that inhibits pain in remote parts of the body. In other words, a descending, endogenous analgesic “pain inhibits pain” mechanism is used.
The initial authorization was based on the results of a randomized, double-blind, sham-controlled, multicenter study involving 252 individuals who were experiencing 2 to 8 migraine headaches per month. Participants were assigned to either a treatment group (n=126), where the device was applied for 30 to 45 minutes within an hour of a migraine attack, or to a sham treatment group (n=126). Investigators looked at migraine pain levels at baseline and at 2 and 48 hours post-treatment, as well as patient-reported most bothersome symptoms. They found that REN provided superior, clinically meaningful relief from migraine pain and the most bothersome symptoms, as follows3:
- 67% of patients in the active treatment group achieved a response at 2 hours vs 39% of individuals in the sham-treatment group
- Pain-free rates at 2 hours in each group were 37% and 18%, respectively
- Most bothersome symptom relief rates at 2 hours were 46% and 22%, respectively
Additionally, pain relief and pain-free responses were sustained at 48 hours. Nearly 40% of active treatment participants still reported pain relief at 48 hours, with pain-free rates at 48 hours in each group of 21% and 8%, respectively. The adverse event rate was low. The most commonly reported adverse event in the active-treatment group was a sensation of warmth (2.4%). Arm pain (1.6%), redness (1.6%), and numbness (0.8%) were also reported in those receiving active treatment.3
In 2020, REN received authorization for the acute treatment of chronic migraine in adults, and the following year authorization was expanded to include adolescent migraine. This development offered a nonpharmacologic treatment approach for migraine sufferers who experience 15 or more headache days per month, which is significant because it reduces the likelihood of medication overuse headache.
Approval for chronic migraine was based on results of an open-label, single-arm, dual-center study involving 38 individuals with chronic migraine. Participants used the device over 4 weeks within 1 hour of a migraine attack. Investigators assessed pain levels at 2 and 24 hours after use; they defined consistency of response as response to at least half of the treatments. The study demonstrated the following4:
- 74% of patients attained pain relief at 2 hours
- 26% were pain free at 2 hours
- 84% achieved sustained pain relief at 24 hours
- 45% achieved sustained pain relief at 24 hours in at least half of their treated attacks
- <2% of participants experienced device-related adverse events
The authors concluded that REN could be used for a series of migraine attacks and is a safe and effective nonpharmacologic approach for individuals who suffer from chronic migraine.4
The findings from these trials are supported by a subsequent trial published earlier this year. This open-label, single-arm study evaluated 91 individuals with chronic migraine who were treated with REN for 4 weeks. Investigators assessed pain levels, associated pain symptoms, and functional disability at baseline as well as at 2 and 24 hours post-treatment. Of the patients in this study5:
- At 2 hours, 59% achieved pain relief, and 21% reported that their pain disappeared
- 73% noted sustained pain relief at 24 hours
- REN was shown to impact nausea, photophobia, and phonophobia favorably, and patients’ functional ability also improved after use
Results from 2 additional trials were also recently released. One study involving 35 adolescents treated with either REN or standard-of-care medications showed REN to be superior with regard to pain freedom (37% vs 9%), consistency of pain freedom (40% vs 9%), pain relief (71% vs 57%), and consistency of pain relief (80% vs 57%).6 The other study included 91 women with a history of menstrual migraine and at least 4 REN treatments. Nearly 75% of patients reported Nerivio to be at least moderately effective, 45% said they were satisfied with the treatment, and all participants noted that it was at least moderately tolerable.7
Combined Occipital and Trigeminal Neuromodulation
In March 2021, the FDA authorized combined occipital and trigeminal neuromodulation (Relivion) for self-treatment of acute migraine.8 It is not yet commercially available, but it will require a prescription. The headset-like device stimulates the occipital and trigeminal nerves by delivering precise modulated pulses simultaneously to 6 branches of the occipital and trigeminal nerves via 3 adaptive output channels. The occipital and trigeminal nerves conduct the signals directly to the brainstem, which maximizes the synergistic effect.9
The results of 2 clinical trials led to FDA approval. These studies have not yet been published in a peer-reviewed journal. The first study, presented at the 61st Annual Scientific Meeting of the American Headache Society in 2019, was a prospective, randomized, double-blind, parallel-group, sham-controlled clinical study involving 55 individuals with chronic or episodic migraine. Participants administered the device for 1 hour soon after migraine onset or administered a sham treatment. Researchers looked at pain score change from baseline to 1 hour post-treatment, as well as pain intensity at baseline and at 1, 2, and 24 hours post-treatment. The study showed that 76% of participants in the active-treatment group experienced headache relief at 2 hours vs 32% in the sham-treatment contingent. No serious adverse events were reported.10 The investigators hypothesized that the positive results observed were a result of the synergistic neuromodulatory effect elicited by concurrent activation of the occipital and trigeminal neural pathways.
Following this study, there was a multi-center, prospective, randomized, double-blind, placebo-controlled clinical trial involving 131 individuals with migraine with or without aura. Participants were assigned to either active treatment or placebo. Investigators assessed reported migraine pain reduction at 2 hours, as well as improvement in most bothersome symptoms after 2 hours, reported pain reduction at 1 hour, and being pain-free at 2 hours. At 2 hours post-treatment11:
- 46% of individuals who were actively treated reached complete freedom from pain vs 12% in the control group
- 75% of active-treatment participants reported being completely free of their most bothersome symptom vs 47% of control patients
- The rates of complete freedom from migraine symptoms were 47% and 11%, respectively
- The rates of pain relief after 2 hours were 60% and 37%, respectively
- No serious adverse events were noted
A systematic review and meta-analysis of 13 studies involving 221 individuals published earlier this year looked at changes in pain scores and response rates to implantable peripheral nerve stimulation for trigeminal neuropathic pain. The response rate to neuromodulation therapy was 61%, the reduction in overall pain scores (2.363) was significant, and a subgroup assessment revealed that the stimulation target (peripheral branch, trigeminal ganglion, or trigeminal nerve root) was responsible for heterogeneity across the studies analyzed. Furthermore, stimulating the trigeminal peripheral branch resulted in better clinical outcomes. The authors noted that their findings reinforce the promise of implantable therapy, particularly for individuals who do not tolerate traditional therapies.12
Looking forward, new data are scheduled to be presented at the International Headache Virtual Congress in September 2021 showing that neuromodulation therapy is highly effective in reducing monthly headache days in individuals who suffer from difficult-to-treat migraine. A larger-scale, double-blind, sham-controlled study is planned to further establish these findings.
Other FDA-Approved Therapies
A number of other devices are available for treatment of migraine headache, including:
- Transcranial magnetic stimulation (TMS). In a randomized trial involving 164 individuals with migraine, 39% of the individuals receiving treatment were pain-free at 2 hours vs 22% of those given sham treatment13
- Noninvasive vagal nerve stimulation (nVNS). This is performed using a handheld device that is controlled by the patient, which preferentially activates afferent A and large B fibers. In a randomized trial involving 243 individuals, pain-free rates at 30, 60, and 120 minutes for patients receiving active treatment were 13%, 21%, and 30%, respectively. Rates for those receiving sham treatment were 4%, 10%, and 20%, respectively.14
- Sumatriptan nasal spray (10 mg) with a permeation enhancer. A randomized phase 2 trial involving 107 individuals found that 44% of participants in the treatment group achieved pain freedom at 2 hours vs 23% who received placebo. The spray appears to work quickly and with fewer adverse events than generic sumatriptan 20 mg nasal spray.15
- Transcutaneous supraorbital nerve stimulation (tSNS). Available without a prescription, there are 3 devices that can treat acute migraine; prevent acute migraine; or both.
Therapies Awaiting FDA Approval
There are several therapeutic options in the pipeline that have not yet been authorized by the FDA.
- Zavegepant (formerly known as vazegepant) nasal spray.16 This third-generation small molecule calcitonin gene-related peptide (CGRP) receptor antagonist has been demonstrated to work as a nasal spray in individuals with migraine. In a phase 1 study, the spray was shown to reach maximal concentration earlier than with other CGRP receptor antagonists.17 A phase 2/3 placebo-controlled trial demonstrated sustained pain freedom from 2 to 48 hours with 5-mg, 10-mg, and 20-mg dosages. The 10-mg and 20-mg doses were statistically superior to placebo on the co-primary endpoints of pain freedom and freedom from most bothersome symptom at 2 hours using a single dose. Sustained pain relief from 2 to 48 hours was seen with the 5-mg and 10-mg dosages18
- Sphenopalatine ganglion (SPG) stimulation. This is a microstimulator that is inserted orally, designed to fit the face, and directly targets SPG. Stimulation is active and controlled by the patient. A randomized, sham-controlled trial evaluated acute pain relief as well as pain freedom and found that those receiving treatment were more than twice as likely to experience pain relief and pain freedom19
- Adhesive dermally applied microneedle system (ADAM). This is a transdermal patch containing microprojections, which can be coated with both large and small molecules. In a randomized trial, 42% of treated participants reported being pain free at 2 hours vs 14% of placebo-treated patients. Rates of freedom from most bothersome symptom were 68% and 43%, respectively20
- Dihydroergotamine (DHE) nasal powder spray and intranasal liquid. Both therapies are awaiting FDA approval. The mucoadhesive powder formulation facilitates rapid drug absorption and is offered in a single-use nasal delivery device. In clinical trials, the spray demonstrated the device’s simplicity, reliability, and ease of use.21 The intranasal liquid is designed to deliver the drug into the vascular-rich upper nasal space. In the phase 3 trial that included 354 patients, 66.3% of patients reported pain relief, 38% of patients reported pain freedom, and 52% had freedom from their most bothersome migraine symptom at 2 hours following their first dose.22
References
1. Rapoport AM. Medication overuse headache: preventive treatment with or without detoxification? Published May 24, 2021. Accessed August 13, 2021. https://www.mdedge.com/migraine-icymi/article/240472/headache-migraine/medication-overuse-headache-preventive-treatment-or
2. How to prescribe Nerivio. Theranica. Accessed August 13, 2021. https://nerivio.co/prescribe/
3. Yarnitsky D, Dodick DW, Grosberg BM, et al. Remote electrical neuromodulation (REN) relieves acute migraine: a randomized, double-blind, placebo-controlled, multicenter trial. Headache. 2019;59(8):1240-1252.
4. Nierenburg H, Vieira JR, Lev N, et al. Remote electrical neuromodulation for the acute treatment of migraine in patients with chronic migraine: an open-label pilot study. Pain Ther. 2020;9(2):531-543.
5. Grosberg B, Lin T, Vizel M, Schim J. Remote electrical neuromodulation for the acute treatment of chronic migraine (2007). Neurology. 2021;96(15 Suppl) 2007.
6. Hershey AD, Irwin S, Rabany L, et al. Comparison of remote electrical neuromodulation (REN) and standard-care medications for acute treatment of migraine in adolescents: a post-hoc analysis. Pain Med. 2021 June 29;pnab197. doi: 10.1093/pm/pnab197. [Epub ahead of print].
7. Nierenburg H, Rabany L, Lin T, et al. Remote electrical neuromodulation (REN) for the acute treatment of menstrual migraine: a retrospective survey study of effectiveness and tolerability. Pain Ther. 2021 Jun 17. doi: 10.1007/s40122-021-00276-7. [Epub ahead of print].
8. Brooks M. FDA clears neuromodulation device for acute migraine pain. Published March 2, 2021. Accessed August 13, 2021. https://www.medscape.com/viewarticle/946700
9. A new ecosystem for brain neuromodulation. Neurolief. Accessed August 13, 2021. https://www.neurolief.com/technology/
10. Daniel O, Tepper SJ. First non-invasive combined occipital & trigeminal nerve stimulation digital therapeutics system for treatment of migraine: a randomized, sham-controlled, double-blind clinical trial. Published 2019. Accessed August 13, 2021. https://www.neurolief.com/wp-content/uploads/2019/07/American-Headache-Society2019-Abstract-Oved-Daniel-Stewart-Tepper.pdf
11. Neurolief announces positive results from RIME clinical study of its brain neuromodulation system for treating acute migraine. BusinessWire. Published January 6, 2021. Accessed August 13, 2021. https://www.businesswire.com/news/home/20210106005510/en/Neurolief-Announces-Positive-Results-From-RIME-Clinical-Study-of-Its-Brain-Neuromodulation-System-for-Treating-Acute-Migraine
12. Ni Y, Yang L, Han R, et al. Implantable peripheral nerve stimulation for trigeminal neuropathic pain: a systematic review and meta-analysis. Neuromodulation. 2021 May 18. doi: 10.1111/ner.13421. [Epub ahead of print].
13. Lipton RB, Dodick DW, Silberstein SD, et al. Single-pulse transcranial magnetic stimulation for acute treatment of migraine with aura: a randomized, double-blind, parallel-group, sham-controlled trial. Lancet Neurol. 2010;9(4):373-380.
14. PRESTO clinical trial overview. electroCore. Published 2018. Accessed August 13, 2021. https://www.electrocore.com/wp-content/themes/wp-starter/includes/images/PRESTO_Clinical_Trial_Fact_Sheet_3.29.18.pdf
15. Lipton RB, Munjal S, Brand-Schieber E, Rapoport AM. DFN-02 (sumatriptan 10 mg with a permeation enhancer) nasal spray vs placebo in the acute treatment of migraine: a double-blind, placebo-controlled study. Headache. 2018;58(5):676-687.
16. Clinical trials. Biohaven Pharmaceuticals. Accessed August 14, 2021. https://www.biohavenpharma.com/science-pipeline/resources/clinical-trials
17. Biohaven achieves targeted therapeutic exposures of BHV-3500, a third-generation small molecule CGRP receptor antagonist. Biohaven Pharmaceuticals. Published February 4, 2019. Accessed August 14, 2021. https://www.biohavenpharma.com/investors/news-events/press-releases/02-04-2019
18. Biohaven achieves positive topline results in pivotal phase 2/3 study of vazegepant, the first and only intranasal CGRP receptor antagonist in clinical development for the acute treatment of migraine. Biospace. Published December 17, 2019. Accessed August 14, 2021. https://www.biospace.com/article/releases/biohaven-achieves-positive-topline-results-in-pivotal-phase-2-3-study-of-vazegepant-the-first-and-only-intranasal-cgrp-receptor-antagonist-in-clinical-development-for-the-acute-treatment-of-migraine/
19. Schoenen J, Jensen RH, Lantéri-Minet M, et al. Stimulation of the sphenopalatine ganglion (SPG) for cluster headache treatment. Pathway CH-1: a randomized, sham-controlled study. Cephalalgia. 2013;33(10):816-830.
20. Spierings EL, Brandes JL, Kudrow DB, et al. Randomized, double-blind, placebo-controlled, parallel-group, multi-center study of the safety and efficacy of ADAM zolmitriptan for the acute treatment of migraine. Cephalalgia. 2018;38(2):215-224.
21. STS101 (DHE Nasal Powder). Satsuma Pharmaceuticals. Accessed August 14, 2021. https://www.satsumarx.com/our-research/sts101/
22. Impel NeuroPharma announces U.S. Food & Drug Administration acceptance of new drug application for INP104 for the acute treatment of migraine. PRNewswire. Published January 20, 2021. Accessed August 14, 2021. https://www.prnewswire.com/news-releases/impel-neuropharma-announces-us-food--drug-administration-acceptance-of-new-drug-application-for-inp104-for-the-acute-treatment-of-migraine-301211380.html
Remote upper arm neuromodulation and combined occipital and trigeminal neuromodulation lead the way as the newest entries to the field, followed by 8 other devices that are now available or are expected to be soon.
The increasing array of prescription medications for the treatment of migraine are welcome additions for patients who suffer from this life-altering condition and the clinicians who treat it; but not all individuals tolerate oral and injectable therapies, and others face the risk of adverse events and medication overuse headache.1 Fortunately, there are a number of devices available to consider, and still others are awaiting approval from the US Food and Drug Administration (FDA).
Two of the most promising devices are remote upper arm neuromodulation (REN) and combined occipital and trigeminal neuromodulation. Here we highlight data from pivotal trials evaluating these 2 treatment options and provide information about other devices worth consideration.
Remote Upper Arm Neuromodulation (REN)
Nerivio was initially authorized by the FDA for the acute treatment of episodic migraine. Available by prescription, the device is administered by the patient at home.2 It stimulates upper arm peripheral nerves, which induces conditioned pain modulation (CPM) that inhibits pain in remote parts of the body. In other words, a descending, endogenous analgesic “pain inhibits pain” mechanism is used.
The initial authorization was based on the results of a randomized, double-blind, sham-controlled, multicenter study involving 252 individuals who were experiencing 2 to 8 migraine headaches per month. Participants were assigned to either a treatment group (n=126), where the device was applied for 30 to 45 minutes within an hour of a migraine attack, or to a sham treatment group (n=126). Investigators looked at migraine pain levels at baseline and at 2 and 48 hours post-treatment, as well as patient-reported most bothersome symptoms. They found that REN provided superior, clinically meaningful relief from migraine pain and the most bothersome symptoms, as follows3:
- 67% of patients in the active treatment group achieved a response at 2 hours vs 39% of individuals in the sham-treatment group
- Pain-free rates at 2 hours in each group were 37% and 18%, respectively
- Most bothersome symptom relief rates at 2 hours were 46% and 22%, respectively
Additionally, pain relief and pain-free responses were sustained at 48 hours. Nearly 40% of active treatment participants still reported pain relief at 48 hours, with pain-free rates at 48 hours in each group of 21% and 8%, respectively. The adverse event rate was low. The most commonly reported adverse event in the active-treatment group was a sensation of warmth (2.4%). Arm pain (1.6%), redness (1.6%), and numbness (0.8%) were also reported in those receiving active treatment.3
In 2020, REN received authorization for the acute treatment of chronic migraine in adults, and the following year authorization was expanded to include adolescent migraine. This development offered a nonpharmacologic treatment approach for migraine sufferers who experience 15 or more headache days per month, which is significant because it reduces the likelihood of medication overuse headache.
Approval for chronic migraine was based on results of an open-label, single-arm, dual-center study involving 38 individuals with chronic migraine. Participants used the device over 4 weeks within 1 hour of a migraine attack. Investigators assessed pain levels at 2 and 24 hours after use; they defined consistency of response as response to at least half of the treatments. The study demonstrated the following4:
- 74% of patients attained pain relief at 2 hours
- 26% were pain free at 2 hours
- 84% achieved sustained pain relief at 24 hours
- 45% achieved sustained pain relief at 24 hours in at least half of their treated attacks
- <2% of participants experienced device-related adverse events
The authors concluded that REN could be used for a series of migraine attacks and is a safe and effective nonpharmacologic approach for individuals who suffer from chronic migraine.4
The findings from these trials are supported by a subsequent trial published earlier this year. This open-label, single-arm study evaluated 91 individuals with chronic migraine who were treated with REN for 4 weeks. Investigators assessed pain levels, associated pain symptoms, and functional disability at baseline as well as at 2 and 24 hours post-treatment. Of the patients in this study5:
- At 2 hours, 59% achieved pain relief, and 21% reported that their pain disappeared
- 73% noted sustained pain relief at 24 hours
- REN was shown to impact nausea, photophobia, and phonophobia favorably, and patients’ functional ability also improved after use
Results from 2 additional trials were also recently released. One study involving 35 adolescents treated with either REN or standard-of-care medications showed REN to be superior with regard to pain freedom (37% vs 9%), consistency of pain freedom (40% vs 9%), pain relief (71% vs 57%), and consistency of pain relief (80% vs 57%).6 The other study included 91 women with a history of menstrual migraine and at least 4 REN treatments. Nearly 75% of patients reported Nerivio to be at least moderately effective, 45% said they were satisfied with the treatment, and all participants noted that it was at least moderately tolerable.7
Combined Occipital and Trigeminal Neuromodulation
In March 2021, the FDA authorized combined occipital and trigeminal neuromodulation (Relivion) for self-treatment of acute migraine.8 It is not yet commercially available, but it will require a prescription. The headset-like device stimulates the occipital and trigeminal nerves by delivering precise modulated pulses simultaneously to 6 branches of the occipital and trigeminal nerves via 3 adaptive output channels. The occipital and trigeminal nerves conduct the signals directly to the brainstem, which maximizes the synergistic effect.9
The results of 2 clinical trials led to FDA approval. These studies have not yet been published in a peer-reviewed journal. The first study, presented at the 61st Annual Scientific Meeting of the American Headache Society in 2019, was a prospective, randomized, double-blind, parallel-group, sham-controlled clinical study involving 55 individuals with chronic or episodic migraine. Participants administered the device for 1 hour soon after migraine onset or administered a sham treatment. Researchers looked at pain score change from baseline to 1 hour post-treatment, as well as pain intensity at baseline and at 1, 2, and 24 hours post-treatment. The study showed that 76% of participants in the active-treatment group experienced headache relief at 2 hours vs 32% in the sham-treatment contingent. No serious adverse events were reported.10 The investigators hypothesized that the positive results observed were a result of the synergistic neuromodulatory effect elicited by concurrent activation of the occipital and trigeminal neural pathways.
Following this study, there was a multi-center, prospective, randomized, double-blind, placebo-controlled clinical trial involving 131 individuals with migraine with or without aura. Participants were assigned to either active treatment or placebo. Investigators assessed reported migraine pain reduction at 2 hours, as well as improvement in most bothersome symptoms after 2 hours, reported pain reduction at 1 hour, and being pain-free at 2 hours. At 2 hours post-treatment11:
- 46% of individuals who were actively treated reached complete freedom from pain vs 12% in the control group
- 75% of active-treatment participants reported being completely free of their most bothersome symptom vs 47% of control patients
- The rates of complete freedom from migraine symptoms were 47% and 11%, respectively
- The rates of pain relief after 2 hours were 60% and 37%, respectively
- No serious adverse events were noted
A systematic review and meta-analysis of 13 studies involving 221 individuals published earlier this year looked at changes in pain scores and response rates to implantable peripheral nerve stimulation for trigeminal neuropathic pain. The response rate to neuromodulation therapy was 61%, the reduction in overall pain scores (2.363) was significant, and a subgroup assessment revealed that the stimulation target (peripheral branch, trigeminal ganglion, or trigeminal nerve root) was responsible for heterogeneity across the studies analyzed. Furthermore, stimulating the trigeminal peripheral branch resulted in better clinical outcomes. The authors noted that their findings reinforce the promise of implantable therapy, particularly for individuals who do not tolerate traditional therapies.12
Looking forward, new data are scheduled to be presented at the International Headache Virtual Congress in September 2021 showing that neuromodulation therapy is highly effective in reducing monthly headache days in individuals who suffer from difficult-to-treat migraine. A larger-scale, double-blind, sham-controlled study is planned to further establish these findings.
Other FDA-Approved Therapies
A number of other devices are available for treatment of migraine headache, including:
- Transcranial magnetic stimulation (TMS). In a randomized trial involving 164 individuals with migraine, 39% of the individuals receiving treatment were pain-free at 2 hours vs 22% of those given sham treatment13
- Noninvasive vagal nerve stimulation (nVNS). This is performed using a handheld device that is controlled by the patient, which preferentially activates afferent A and large B fibers. In a randomized trial involving 243 individuals, pain-free rates at 30, 60, and 120 minutes for patients receiving active treatment were 13%, 21%, and 30%, respectively. Rates for those receiving sham treatment were 4%, 10%, and 20%, respectively.14
- Sumatriptan nasal spray (10 mg) with a permeation enhancer. A randomized phase 2 trial involving 107 individuals found that 44% of participants in the treatment group achieved pain freedom at 2 hours vs 23% who received placebo. The spray appears to work quickly and with fewer adverse events than generic sumatriptan 20 mg nasal spray.15
- Transcutaneous supraorbital nerve stimulation (tSNS). Available without a prescription, there are 3 devices that can treat acute migraine; prevent acute migraine; or both.
Therapies Awaiting FDA Approval
There are several therapeutic options in the pipeline that have not yet been authorized by the FDA.
- Zavegepant (formerly known as vazegepant) nasal spray.16 This third-generation small molecule calcitonin gene-related peptide (CGRP) receptor antagonist has been demonstrated to work as a nasal spray in individuals with migraine. In a phase 1 study, the spray was shown to reach maximal concentration earlier than with other CGRP receptor antagonists.17 A phase 2/3 placebo-controlled trial demonstrated sustained pain freedom from 2 to 48 hours with 5-mg, 10-mg, and 20-mg dosages. The 10-mg and 20-mg doses were statistically superior to placebo on the co-primary endpoints of pain freedom and freedom from most bothersome symptom at 2 hours using a single dose. Sustained pain relief from 2 to 48 hours was seen with the 5-mg and 10-mg dosages18
- Sphenopalatine ganglion (SPG) stimulation. This is a microstimulator that is inserted orally, designed to fit the face, and directly targets SPG. Stimulation is active and controlled by the patient. A randomized, sham-controlled trial evaluated acute pain relief as well as pain freedom and found that those receiving treatment were more than twice as likely to experience pain relief and pain freedom19
- Adhesive dermally applied microneedle system (ADAM). This is a transdermal patch containing microprojections, which can be coated with both large and small molecules. In a randomized trial, 42% of treated participants reported being pain free at 2 hours vs 14% of placebo-treated patients. Rates of freedom from most bothersome symptom were 68% and 43%, respectively20
- Dihydroergotamine (DHE) nasal powder spray and intranasal liquid. Both therapies are awaiting FDA approval. The mucoadhesive powder formulation facilitates rapid drug absorption and is offered in a single-use nasal delivery device. In clinical trials, the spray demonstrated the device’s simplicity, reliability, and ease of use.21 The intranasal liquid is designed to deliver the drug into the vascular-rich upper nasal space. In the phase 3 trial that included 354 patients, 66.3% of patients reported pain relief, 38% of patients reported pain freedom, and 52% had freedom from their most bothersome migraine symptom at 2 hours following their first dose.22
Remote upper arm neuromodulation and combined occipital and trigeminal neuromodulation lead the way as the newest entries to the field, followed by 8 other devices that are now available or are expected to be soon.
The increasing array of prescription medications for the treatment of migraine are welcome additions for patients who suffer from this life-altering condition and the clinicians who treat it; but not all individuals tolerate oral and injectable therapies, and others face the risk of adverse events and medication overuse headache.1 Fortunately, there are a number of devices available to consider, and still others are awaiting approval from the US Food and Drug Administration (FDA).
Two of the most promising devices are remote upper arm neuromodulation (REN) and combined occipital and trigeminal neuromodulation. Here we highlight data from pivotal trials evaluating these 2 treatment options and provide information about other devices worth consideration.
Remote Upper Arm Neuromodulation (REN)
Nerivio was initially authorized by the FDA for the acute treatment of episodic migraine. Available by prescription, the device is administered by the patient at home.2 It stimulates upper arm peripheral nerves, which induces conditioned pain modulation (CPM) that inhibits pain in remote parts of the body. In other words, a descending, endogenous analgesic “pain inhibits pain” mechanism is used.
The initial authorization was based on the results of a randomized, double-blind, sham-controlled, multicenter study involving 252 individuals who were experiencing 2 to 8 migraine headaches per month. Participants were assigned to either a treatment group (n=126), where the device was applied for 30 to 45 minutes within an hour of a migraine attack, or to a sham treatment group (n=126). Investigators looked at migraine pain levels at baseline and at 2 and 48 hours post-treatment, as well as patient-reported most bothersome symptoms. They found that REN provided superior, clinically meaningful relief from migraine pain and the most bothersome symptoms, as follows3:
- 67% of patients in the active treatment group achieved a response at 2 hours vs 39% of individuals in the sham-treatment group
- Pain-free rates at 2 hours in each group were 37% and 18%, respectively
- Most bothersome symptom relief rates at 2 hours were 46% and 22%, respectively
Additionally, pain relief and pain-free responses were sustained at 48 hours. Nearly 40% of active treatment participants still reported pain relief at 48 hours, with pain-free rates at 48 hours in each group of 21% and 8%, respectively. The adverse event rate was low. The most commonly reported adverse event in the active-treatment group was a sensation of warmth (2.4%). Arm pain (1.6%), redness (1.6%), and numbness (0.8%) were also reported in those receiving active treatment.3
In 2020, REN received authorization for the acute treatment of chronic migraine in adults, and the following year authorization was expanded to include adolescent migraine. This development offered a nonpharmacologic treatment approach for migraine sufferers who experience 15 or more headache days per month, which is significant because it reduces the likelihood of medication overuse headache.
Approval for chronic migraine was based on results of an open-label, single-arm, dual-center study involving 38 individuals with chronic migraine. Participants used the device over 4 weeks within 1 hour of a migraine attack. Investigators assessed pain levels at 2 and 24 hours after use; they defined consistency of response as response to at least half of the treatments. The study demonstrated the following4:
- 74% of patients attained pain relief at 2 hours
- 26% were pain free at 2 hours
- 84% achieved sustained pain relief at 24 hours
- 45% achieved sustained pain relief at 24 hours in at least half of their treated attacks
- <2% of participants experienced device-related adverse events
The authors concluded that REN could be used for a series of migraine attacks and is a safe and effective nonpharmacologic approach for individuals who suffer from chronic migraine.4
The findings from these trials are supported by a subsequent trial published earlier this year. This open-label, single-arm study evaluated 91 individuals with chronic migraine who were treated with REN for 4 weeks. Investigators assessed pain levels, associated pain symptoms, and functional disability at baseline as well as at 2 and 24 hours post-treatment. Of the patients in this study5:
- At 2 hours, 59% achieved pain relief, and 21% reported that their pain disappeared
- 73% noted sustained pain relief at 24 hours
- REN was shown to impact nausea, photophobia, and phonophobia favorably, and patients’ functional ability also improved after use
Results from 2 additional trials were also recently released. One study involving 35 adolescents treated with either REN or standard-of-care medications showed REN to be superior with regard to pain freedom (37% vs 9%), consistency of pain freedom (40% vs 9%), pain relief (71% vs 57%), and consistency of pain relief (80% vs 57%).6 The other study included 91 women with a history of menstrual migraine and at least 4 REN treatments. Nearly 75% of patients reported Nerivio to be at least moderately effective, 45% said they were satisfied with the treatment, and all participants noted that it was at least moderately tolerable.7
Combined Occipital and Trigeminal Neuromodulation
In March 2021, the FDA authorized combined occipital and trigeminal neuromodulation (Relivion) for self-treatment of acute migraine.8 It is not yet commercially available, but it will require a prescription. The headset-like device stimulates the occipital and trigeminal nerves by delivering precise modulated pulses simultaneously to 6 branches of the occipital and trigeminal nerves via 3 adaptive output channels. The occipital and trigeminal nerves conduct the signals directly to the brainstem, which maximizes the synergistic effect.9
The results of 2 clinical trials led to FDA approval. These studies have not yet been published in a peer-reviewed journal. The first study, presented at the 61st Annual Scientific Meeting of the American Headache Society in 2019, was a prospective, randomized, double-blind, parallel-group, sham-controlled clinical study involving 55 individuals with chronic or episodic migraine. Participants administered the device for 1 hour soon after migraine onset or administered a sham treatment. Researchers looked at pain score change from baseline to 1 hour post-treatment, as well as pain intensity at baseline and at 1, 2, and 24 hours post-treatment. The study showed that 76% of participants in the active-treatment group experienced headache relief at 2 hours vs 32% in the sham-treatment contingent. No serious adverse events were reported.10 The investigators hypothesized that the positive results observed were a result of the synergistic neuromodulatory effect elicited by concurrent activation of the occipital and trigeminal neural pathways.
Following this study, there was a multi-center, prospective, randomized, double-blind, placebo-controlled clinical trial involving 131 individuals with migraine with or without aura. Participants were assigned to either active treatment or placebo. Investigators assessed reported migraine pain reduction at 2 hours, as well as improvement in most bothersome symptoms after 2 hours, reported pain reduction at 1 hour, and being pain-free at 2 hours. At 2 hours post-treatment11:
- 46% of individuals who were actively treated reached complete freedom from pain vs 12% in the control group
- 75% of active-treatment participants reported being completely free of their most bothersome symptom vs 47% of control patients
- The rates of complete freedom from migraine symptoms were 47% and 11%, respectively
- The rates of pain relief after 2 hours were 60% and 37%, respectively
- No serious adverse events were noted
A systematic review and meta-analysis of 13 studies involving 221 individuals published earlier this year looked at changes in pain scores and response rates to implantable peripheral nerve stimulation for trigeminal neuropathic pain. The response rate to neuromodulation therapy was 61%, the reduction in overall pain scores (2.363) was significant, and a subgroup assessment revealed that the stimulation target (peripheral branch, trigeminal ganglion, or trigeminal nerve root) was responsible for heterogeneity across the studies analyzed. Furthermore, stimulating the trigeminal peripheral branch resulted in better clinical outcomes. The authors noted that their findings reinforce the promise of implantable therapy, particularly for individuals who do not tolerate traditional therapies.12
Looking forward, new data are scheduled to be presented at the International Headache Virtual Congress in September 2021 showing that neuromodulation therapy is highly effective in reducing monthly headache days in individuals who suffer from difficult-to-treat migraine. A larger-scale, double-blind, sham-controlled study is planned to further establish these findings.
Other FDA-Approved Therapies
A number of other devices are available for treatment of migraine headache, including:
- Transcranial magnetic stimulation (TMS). In a randomized trial involving 164 individuals with migraine, 39% of the individuals receiving treatment were pain-free at 2 hours vs 22% of those given sham treatment13
- Noninvasive vagal nerve stimulation (nVNS). This is performed using a handheld device that is controlled by the patient, which preferentially activates afferent A and large B fibers. In a randomized trial involving 243 individuals, pain-free rates at 30, 60, and 120 minutes for patients receiving active treatment were 13%, 21%, and 30%, respectively. Rates for those receiving sham treatment were 4%, 10%, and 20%, respectively.14
- Sumatriptan nasal spray (10 mg) with a permeation enhancer. A randomized phase 2 trial involving 107 individuals found that 44% of participants in the treatment group achieved pain freedom at 2 hours vs 23% who received placebo. The spray appears to work quickly and with fewer adverse events than generic sumatriptan 20 mg nasal spray.15
- Transcutaneous supraorbital nerve stimulation (tSNS). Available without a prescription, there are 3 devices that can treat acute migraine; prevent acute migraine; or both.
Therapies Awaiting FDA Approval
There are several therapeutic options in the pipeline that have not yet been authorized by the FDA.
- Zavegepant (formerly known as vazegepant) nasal spray.16 This third-generation small molecule calcitonin gene-related peptide (CGRP) receptor antagonist has been demonstrated to work as a nasal spray in individuals with migraine. In a phase 1 study, the spray was shown to reach maximal concentration earlier than with other CGRP receptor antagonists.17 A phase 2/3 placebo-controlled trial demonstrated sustained pain freedom from 2 to 48 hours with 5-mg, 10-mg, and 20-mg dosages. The 10-mg and 20-mg doses were statistically superior to placebo on the co-primary endpoints of pain freedom and freedom from most bothersome symptom at 2 hours using a single dose. Sustained pain relief from 2 to 48 hours was seen with the 5-mg and 10-mg dosages18
- Sphenopalatine ganglion (SPG) stimulation. This is a microstimulator that is inserted orally, designed to fit the face, and directly targets SPG. Stimulation is active and controlled by the patient. A randomized, sham-controlled trial evaluated acute pain relief as well as pain freedom and found that those receiving treatment were more than twice as likely to experience pain relief and pain freedom19
- Adhesive dermally applied microneedle system (ADAM). This is a transdermal patch containing microprojections, which can be coated with both large and small molecules. In a randomized trial, 42% of treated participants reported being pain free at 2 hours vs 14% of placebo-treated patients. Rates of freedom from most bothersome symptom were 68% and 43%, respectively20
- Dihydroergotamine (DHE) nasal powder spray and intranasal liquid. Both therapies are awaiting FDA approval. The mucoadhesive powder formulation facilitates rapid drug absorption and is offered in a single-use nasal delivery device. In clinical trials, the spray demonstrated the device’s simplicity, reliability, and ease of use.21 The intranasal liquid is designed to deliver the drug into the vascular-rich upper nasal space. In the phase 3 trial that included 354 patients, 66.3% of patients reported pain relief, 38% of patients reported pain freedom, and 52% had freedom from their most bothersome migraine symptom at 2 hours following their first dose.22
References
1. Rapoport AM. Medication overuse headache: preventive treatment with or without detoxification? Published May 24, 2021. Accessed August 13, 2021. https://www.mdedge.com/migraine-icymi/article/240472/headache-migraine/medication-overuse-headache-preventive-treatment-or
2. How to prescribe Nerivio. Theranica. Accessed August 13, 2021. https://nerivio.co/prescribe/
3. Yarnitsky D, Dodick DW, Grosberg BM, et al. Remote electrical neuromodulation (REN) relieves acute migraine: a randomized, double-blind, placebo-controlled, multicenter trial. Headache. 2019;59(8):1240-1252.
4. Nierenburg H, Vieira JR, Lev N, et al. Remote electrical neuromodulation for the acute treatment of migraine in patients with chronic migraine: an open-label pilot study. Pain Ther. 2020;9(2):531-543.
5. Grosberg B, Lin T, Vizel M, Schim J. Remote electrical neuromodulation for the acute treatment of chronic migraine (2007). Neurology. 2021;96(15 Suppl) 2007.
6. Hershey AD, Irwin S, Rabany L, et al. Comparison of remote electrical neuromodulation (REN) and standard-care medications for acute treatment of migraine in adolescents: a post-hoc analysis. Pain Med. 2021 June 29;pnab197. doi: 10.1093/pm/pnab197. [Epub ahead of print].
7. Nierenburg H, Rabany L, Lin T, et al. Remote electrical neuromodulation (REN) for the acute treatment of menstrual migraine: a retrospective survey study of effectiveness and tolerability. Pain Ther. 2021 Jun 17. doi: 10.1007/s40122-021-00276-7. [Epub ahead of print].
8. Brooks M. FDA clears neuromodulation device for acute migraine pain. Published March 2, 2021. Accessed August 13, 2021. https://www.medscape.com/viewarticle/946700
9. A new ecosystem for brain neuromodulation. Neurolief. Accessed August 13, 2021. https://www.neurolief.com/technology/
10. Daniel O, Tepper SJ. First non-invasive combined occipital & trigeminal nerve stimulation digital therapeutics system for treatment of migraine: a randomized, sham-controlled, double-blind clinical trial. Published 2019. Accessed August 13, 2021. https://www.neurolief.com/wp-content/uploads/2019/07/American-Headache-Society2019-Abstract-Oved-Daniel-Stewart-Tepper.pdf
11. Neurolief announces positive results from RIME clinical study of its brain neuromodulation system for treating acute migraine. BusinessWire. Published January 6, 2021. Accessed August 13, 2021. https://www.businesswire.com/news/home/20210106005510/en/Neurolief-Announces-Positive-Results-From-RIME-Clinical-Study-of-Its-Brain-Neuromodulation-System-for-Treating-Acute-Migraine
12. Ni Y, Yang L, Han R, et al. Implantable peripheral nerve stimulation for trigeminal neuropathic pain: a systematic review and meta-analysis. Neuromodulation. 2021 May 18. doi: 10.1111/ner.13421. [Epub ahead of print].
13. Lipton RB, Dodick DW, Silberstein SD, et al. Single-pulse transcranial magnetic stimulation for acute treatment of migraine with aura: a randomized, double-blind, parallel-group, sham-controlled trial. Lancet Neurol. 2010;9(4):373-380.
14. PRESTO clinical trial overview. electroCore. Published 2018. Accessed August 13, 2021. https://www.electrocore.com/wp-content/themes/wp-starter/includes/images/PRESTO_Clinical_Trial_Fact_Sheet_3.29.18.pdf
15. Lipton RB, Munjal S, Brand-Schieber E, Rapoport AM. DFN-02 (sumatriptan 10 mg with a permeation enhancer) nasal spray vs placebo in the acute treatment of migraine: a double-blind, placebo-controlled study. Headache. 2018;58(5):676-687.
16. Clinical trials. Biohaven Pharmaceuticals. Accessed August 14, 2021. https://www.biohavenpharma.com/science-pipeline/resources/clinical-trials
17. Biohaven achieves targeted therapeutic exposures of BHV-3500, a third-generation small molecule CGRP receptor antagonist. Biohaven Pharmaceuticals. Published February 4, 2019. Accessed August 14, 2021. https://www.biohavenpharma.com/investors/news-events/press-releases/02-04-2019
18. Biohaven achieves positive topline results in pivotal phase 2/3 study of vazegepant, the first and only intranasal CGRP receptor antagonist in clinical development for the acute treatment of migraine. Biospace. Published December 17, 2019. Accessed August 14, 2021. https://www.biospace.com/article/releases/biohaven-achieves-positive-topline-results-in-pivotal-phase-2-3-study-of-vazegepant-the-first-and-only-intranasal-cgrp-receptor-antagonist-in-clinical-development-for-the-acute-treatment-of-migraine/
19. Schoenen J, Jensen RH, Lantéri-Minet M, et al. Stimulation of the sphenopalatine ganglion (SPG) for cluster headache treatment. Pathway CH-1: a randomized, sham-controlled study. Cephalalgia. 2013;33(10):816-830.
20. Spierings EL, Brandes JL, Kudrow DB, et al. Randomized, double-blind, placebo-controlled, parallel-group, multi-center study of the safety and efficacy of ADAM zolmitriptan for the acute treatment of migraine. Cephalalgia. 2018;38(2):215-224.
21. STS101 (DHE Nasal Powder). Satsuma Pharmaceuticals. Accessed August 14, 2021. https://www.satsumarx.com/our-research/sts101/
22. Impel NeuroPharma announces U.S. Food & Drug Administration acceptance of new drug application for INP104 for the acute treatment of migraine. PRNewswire. Published January 20, 2021. Accessed August 14, 2021. https://www.prnewswire.com/news-releases/impel-neuropharma-announces-us-food--drug-administration-acceptance-of-new-drug-application-for-inp104-for-the-acute-treatment-of-migraine-301211380.html
References
1. Rapoport AM. Medication overuse headache: preventive treatment with or without detoxification? Published May 24, 2021. Accessed August 13, 2021. https://www.mdedge.com/migraine-icymi/article/240472/headache-migraine/medication-overuse-headache-preventive-treatment-or
2. How to prescribe Nerivio. Theranica. Accessed August 13, 2021. https://nerivio.co/prescribe/
3. Yarnitsky D, Dodick DW, Grosberg BM, et al. Remote electrical neuromodulation (REN) relieves acute migraine: a randomized, double-blind, placebo-controlled, multicenter trial. Headache. 2019;59(8):1240-1252.
4. Nierenburg H, Vieira JR, Lev N, et al. Remote electrical neuromodulation for the acute treatment of migraine in patients with chronic migraine: an open-label pilot study. Pain Ther. 2020;9(2):531-543.
5. Grosberg B, Lin T, Vizel M, Schim J. Remote electrical neuromodulation for the acute treatment of chronic migraine (2007). Neurology. 2021;96(15 Suppl) 2007.
6. Hershey AD, Irwin S, Rabany L, et al. Comparison of remote electrical neuromodulation (REN) and standard-care medications for acute treatment of migraine in adolescents: a post-hoc analysis. Pain Med. 2021 June 29;pnab197. doi: 10.1093/pm/pnab197. [Epub ahead of print].
7. Nierenburg H, Rabany L, Lin T, et al. Remote electrical neuromodulation (REN) for the acute treatment of menstrual migraine: a retrospective survey study of effectiveness and tolerability. Pain Ther. 2021 Jun 17. doi: 10.1007/s40122-021-00276-7. [Epub ahead of print].
8. Brooks M. FDA clears neuromodulation device for acute migraine pain. Published March 2, 2021. Accessed August 13, 2021. https://www.medscape.com/viewarticle/946700
9. A new ecosystem for brain neuromodulation. Neurolief. Accessed August 13, 2021. https://www.neurolief.com/technology/
10. Daniel O, Tepper SJ. First non-invasive combined occipital & trigeminal nerve stimulation digital therapeutics system for treatment of migraine: a randomized, sham-controlled, double-blind clinical trial. Published 2019. Accessed August 13, 2021. https://www.neurolief.com/wp-content/uploads/2019/07/American-Headache-Society2019-Abstract-Oved-Daniel-Stewart-Tepper.pdf
11. Neurolief announces positive results from RIME clinical study of its brain neuromodulation system for treating acute migraine. BusinessWire. Published January 6, 2021. Accessed August 13, 2021. https://www.businesswire.com/news/home/20210106005510/en/Neurolief-Announces-Positive-Results-From-RIME-Clinical-Study-of-Its-Brain-Neuromodulation-System-for-Treating-Acute-Migraine
12. Ni Y, Yang L, Han R, et al. Implantable peripheral nerve stimulation for trigeminal neuropathic pain: a systematic review and meta-analysis. Neuromodulation. 2021 May 18. doi: 10.1111/ner.13421. [Epub ahead of print].
13. Lipton RB, Dodick DW, Silberstein SD, et al. Single-pulse transcranial magnetic stimulation for acute treatment of migraine with aura: a randomized, double-blind, parallel-group, sham-controlled trial. Lancet Neurol. 2010;9(4):373-380.
14. PRESTO clinical trial overview. electroCore. Published 2018. Accessed August 13, 2021. https://www.electrocore.com/wp-content/themes/wp-starter/includes/images/PRESTO_Clinical_Trial_Fact_Sheet_3.29.18.pdf
15. Lipton RB, Munjal S, Brand-Schieber E, Rapoport AM. DFN-02 (sumatriptan 10 mg with a permeation enhancer) nasal spray vs placebo in the acute treatment of migraine: a double-blind, placebo-controlled study. Headache. 2018;58(5):676-687.
16. Clinical trials. Biohaven Pharmaceuticals. Accessed August 14, 2021. https://www.biohavenpharma.com/science-pipeline/resources/clinical-trials
17. Biohaven achieves targeted therapeutic exposures of BHV-3500, a third-generation small molecule CGRP receptor antagonist. Biohaven Pharmaceuticals. Published February 4, 2019. Accessed August 14, 2021. https://www.biohavenpharma.com/investors/news-events/press-releases/02-04-2019
18. Biohaven achieves positive topline results in pivotal phase 2/3 study of vazegepant, the first and only intranasal CGRP receptor antagonist in clinical development for the acute treatment of migraine. Biospace. Published December 17, 2019. Accessed August 14, 2021. https://www.biospace.com/article/releases/biohaven-achieves-positive-topline-results-in-pivotal-phase-2-3-study-of-vazegepant-the-first-and-only-intranasal-cgrp-receptor-antagonist-in-clinical-development-for-the-acute-treatment-of-migraine/
19. Schoenen J, Jensen RH, Lantéri-Minet M, et al. Stimulation of the sphenopalatine ganglion (SPG) for cluster headache treatment. Pathway CH-1: a randomized, sham-controlled study. Cephalalgia. 2013;33(10):816-830.
20. Spierings EL, Brandes JL, Kudrow DB, et al. Randomized, double-blind, placebo-controlled, parallel-group, multi-center study of the safety and efficacy of ADAM zolmitriptan for the acute treatment of migraine. Cephalalgia. 2018;38(2):215-224.
21. STS101 (DHE Nasal Powder). Satsuma Pharmaceuticals. Accessed August 14, 2021. https://www.satsumarx.com/our-research/sts101/
22. Impel NeuroPharma announces U.S. Food & Drug Administration acceptance of new drug application for INP104 for the acute treatment of migraine. PRNewswire. Published January 20, 2021. Accessed August 14, 2021. https://www.prnewswire.com/news-releases/impel-neuropharma-announces-us-food--drug-administration-acceptance-of-new-drug-application-for-inp104-for-the-acute-treatment-of-migraine-301211380.html
Trial finds that intranasal DHE is well tolerated and may reduce migraine symptoms
, a new study suggests.
A phase 3, open-label trial of INP104, or Trudhesa – Impel NeuroPharma’s proprietary Precision Olfactory Delivery of DHE – found that most patients experienced symptom relief within 2 hours and reported that the medication was easy to use and preferable to their current therapy.
Another treatment option?
Of about 18 million diagnosed migraine patients in the United States, 4 million receive prescription treatment. Nearly 80% of migraine therapies involve triptans, but 30%-40% of patients don’t find adequate relief with triptans. Moreover, the majority of patients who do respond to triptans report that they’d like to try a different therapy.
“INP104 has the potential to deliver rapid symptom relief, without injection, that is well tolerated and suitable for outpatient us,” lead author Timothy Smith, MD, of StudyMetrix Research, St. Louis, and colleagues wrote in the paper.
The results were published online Aug. 7 in Headache.
A total of 360 patients aged 18-65 years with a diagnosis of migraine with or without aura with at least two attacks per month over the course of the previous 6 months were enrolled in the 24-week safety study, which had a 28-week extension period. Participants used their “best usual care” to treat their migraines during the initial 28-day screening period. Afterward, they were given 1.45-mg doses of INP04 to self-administer into the upper nasal space to treat self-recognized attacks. No more than two doses per 24 hours and three doses per 7 days were allowed. The Full Safety Set analysis comprised 354 patients who dosed at least once. The Primary Safety Set involved 185 patients who administered an average of two or more doses per 28-day period during the 24-week treatment period. A total of 4,515 self-recognized migraines were treated during the 24-week period; 6,332 doses of INP04 were analyzed.
Nearly 37% (130/354) of patients reported treatment-emergent adverse events (TEAEs); 6.8% (24/354) discontinued treatment because of the TEAEs over the 24 weeks. The most common TEAE was nasal congestion (15%, 53/354), followed by nausea (6.8%, 24/354).
Within an hour of INP104 administration, 47.6% of patients reported pain relief. After 2 hours of INP104 administration, 38% reported pain freedom and 66.3% reported pain relief. Headache recurrence was observed in 7.1% and 14.3% of patients at 24 and 48 hours, respectively.
In a questionnaire, 84% of patients agreed or strongly agreed that INP04 was easy to use. Most reported that INP104 slowed the recurrence of their migraines and was more rapidly and consistently effective than their previous best usual care treatment.
Intranasal delivery of DHE was developed in response to the challenges of traditional IV administration.
“While intravenous (IV) dihydroergotamine (DHE) mesylate has a long, established history as an effective migraine therapy, its use as an acute treatment can be limited by the high rate of nausea and vomiting reported by patients, which often requires pretreatment with antiemetics,” Dr. Smith and colleagues wrote. “Furthermore, IV DHE mesylate needs to be administered in emergency room settings or by headache specialists, limiting convenience.”
A novel delivery system
“There’s already a nasal spray on the market right now which doesn’t seem to work that well in a large number of people. This device [INP04] was designed to get the same substances to a part of the nose that’s higher and farther back, where there may be better absorption,” said Alan Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles, said in an interview. Dr. Rapoport was not involved with the study.
The proprietary Precision Olfactory Delivery (POD) is meant to improve on current nasal delivery methods such as sprays, droppers, and pumps, which may deliver “less than 5% of the active drug to the upper nasal space,” according to a press release from Impel NeuroPharma.
Nasal delivery also may have advantages over oral medications. People with migraines may be more likely to have gastroparesis – delayed stomach emptying – which may affect their ability to absorb oral medications and delay symptom relief. However, patients may hesitate to agree to a medication that involves nasal delivery, Dr. Rapoport said.
“I will say it’s a little more difficult getting your patients to take a nasal spray,” Dr. Rapoport said. “Patients are used to taking tablets for their headaches,” he said. “But if the doctor spends a little more time with the patient and says, ‘Look, this could work faster for your migraine as a nasal spray. Why don’t you try it a couple of times and see if you like it or not?’ patients are usually willing to give it a try.”
The study’s limitations include the lack of a control group given that it was an open-label trial. It was carried out at 38 sites in one geographical area, which may affect the generalizability of the results. The study did not assess patients with new-onset migraine or chronic migraine.
The Food and Drug Administration approved Trudhesa on Sept. 2, 2021.
The study was funded by Impel NeuroPharma. Dr. Smith has received funding from a number of pharmaceutical companies. Dr. Rapoport disclosed no relevant financial relationships.
, a new study suggests.
A phase 3, open-label trial of INP104, or Trudhesa – Impel NeuroPharma’s proprietary Precision Olfactory Delivery of DHE – found that most patients experienced symptom relief within 2 hours and reported that the medication was easy to use and preferable to their current therapy.
Another treatment option?
Of about 18 million diagnosed migraine patients in the United States, 4 million receive prescription treatment. Nearly 80% of migraine therapies involve triptans, but 30%-40% of patients don’t find adequate relief with triptans. Moreover, the majority of patients who do respond to triptans report that they’d like to try a different therapy.
“INP104 has the potential to deliver rapid symptom relief, without injection, that is well tolerated and suitable for outpatient us,” lead author Timothy Smith, MD, of StudyMetrix Research, St. Louis, and colleagues wrote in the paper.
The results were published online Aug. 7 in Headache.
A total of 360 patients aged 18-65 years with a diagnosis of migraine with or without aura with at least two attacks per month over the course of the previous 6 months were enrolled in the 24-week safety study, which had a 28-week extension period. Participants used their “best usual care” to treat their migraines during the initial 28-day screening period. Afterward, they were given 1.45-mg doses of INP04 to self-administer into the upper nasal space to treat self-recognized attacks. No more than two doses per 24 hours and three doses per 7 days were allowed. The Full Safety Set analysis comprised 354 patients who dosed at least once. The Primary Safety Set involved 185 patients who administered an average of two or more doses per 28-day period during the 24-week treatment period. A total of 4,515 self-recognized migraines were treated during the 24-week period; 6,332 doses of INP04 were analyzed.
Nearly 37% (130/354) of patients reported treatment-emergent adverse events (TEAEs); 6.8% (24/354) discontinued treatment because of the TEAEs over the 24 weeks. The most common TEAE was nasal congestion (15%, 53/354), followed by nausea (6.8%, 24/354).
Within an hour of INP104 administration, 47.6% of patients reported pain relief. After 2 hours of INP104 administration, 38% reported pain freedom and 66.3% reported pain relief. Headache recurrence was observed in 7.1% and 14.3% of patients at 24 and 48 hours, respectively.
In a questionnaire, 84% of patients agreed or strongly agreed that INP04 was easy to use. Most reported that INP104 slowed the recurrence of their migraines and was more rapidly and consistently effective than their previous best usual care treatment.
Intranasal delivery of DHE was developed in response to the challenges of traditional IV administration.
“While intravenous (IV) dihydroergotamine (DHE) mesylate has a long, established history as an effective migraine therapy, its use as an acute treatment can be limited by the high rate of nausea and vomiting reported by patients, which often requires pretreatment with antiemetics,” Dr. Smith and colleagues wrote. “Furthermore, IV DHE mesylate needs to be administered in emergency room settings or by headache specialists, limiting convenience.”
A novel delivery system
“There’s already a nasal spray on the market right now which doesn’t seem to work that well in a large number of people. This device [INP04] was designed to get the same substances to a part of the nose that’s higher and farther back, where there may be better absorption,” said Alan Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles, said in an interview. Dr. Rapoport was not involved with the study.
The proprietary Precision Olfactory Delivery (POD) is meant to improve on current nasal delivery methods such as sprays, droppers, and pumps, which may deliver “less than 5% of the active drug to the upper nasal space,” according to a press release from Impel NeuroPharma.
Nasal delivery also may have advantages over oral medications. People with migraines may be more likely to have gastroparesis – delayed stomach emptying – which may affect their ability to absorb oral medications and delay symptom relief. However, patients may hesitate to agree to a medication that involves nasal delivery, Dr. Rapoport said.
“I will say it’s a little more difficult getting your patients to take a nasal spray,” Dr. Rapoport said. “Patients are used to taking tablets for their headaches,” he said. “But if the doctor spends a little more time with the patient and says, ‘Look, this could work faster for your migraine as a nasal spray. Why don’t you try it a couple of times and see if you like it or not?’ patients are usually willing to give it a try.”
The study’s limitations include the lack of a control group given that it was an open-label trial. It was carried out at 38 sites in one geographical area, which may affect the generalizability of the results. The study did not assess patients with new-onset migraine or chronic migraine.
The Food and Drug Administration approved Trudhesa on Sept. 2, 2021.
The study was funded by Impel NeuroPharma. Dr. Smith has received funding from a number of pharmaceutical companies. Dr. Rapoport disclosed no relevant financial relationships.
, a new study suggests.
A phase 3, open-label trial of INP104, or Trudhesa – Impel NeuroPharma’s proprietary Precision Olfactory Delivery of DHE – found that most patients experienced symptom relief within 2 hours and reported that the medication was easy to use and preferable to their current therapy.
Another treatment option?
Of about 18 million diagnosed migraine patients in the United States, 4 million receive prescription treatment. Nearly 80% of migraine therapies involve triptans, but 30%-40% of patients don’t find adequate relief with triptans. Moreover, the majority of patients who do respond to triptans report that they’d like to try a different therapy.
“INP104 has the potential to deliver rapid symptom relief, without injection, that is well tolerated and suitable for outpatient us,” lead author Timothy Smith, MD, of StudyMetrix Research, St. Louis, and colleagues wrote in the paper.
The results were published online Aug. 7 in Headache.
A total of 360 patients aged 18-65 years with a diagnosis of migraine with or without aura with at least two attacks per month over the course of the previous 6 months were enrolled in the 24-week safety study, which had a 28-week extension period. Participants used their “best usual care” to treat their migraines during the initial 28-day screening period. Afterward, they were given 1.45-mg doses of INP04 to self-administer into the upper nasal space to treat self-recognized attacks. No more than two doses per 24 hours and three doses per 7 days were allowed. The Full Safety Set analysis comprised 354 patients who dosed at least once. The Primary Safety Set involved 185 patients who administered an average of two or more doses per 28-day period during the 24-week treatment period. A total of 4,515 self-recognized migraines were treated during the 24-week period; 6,332 doses of INP04 were analyzed.
Nearly 37% (130/354) of patients reported treatment-emergent adverse events (TEAEs); 6.8% (24/354) discontinued treatment because of the TEAEs over the 24 weeks. The most common TEAE was nasal congestion (15%, 53/354), followed by nausea (6.8%, 24/354).
Within an hour of INP104 administration, 47.6% of patients reported pain relief. After 2 hours of INP104 administration, 38% reported pain freedom and 66.3% reported pain relief. Headache recurrence was observed in 7.1% and 14.3% of patients at 24 and 48 hours, respectively.
In a questionnaire, 84% of patients agreed or strongly agreed that INP04 was easy to use. Most reported that INP104 slowed the recurrence of their migraines and was more rapidly and consistently effective than their previous best usual care treatment.
Intranasal delivery of DHE was developed in response to the challenges of traditional IV administration.
“While intravenous (IV) dihydroergotamine (DHE) mesylate has a long, established history as an effective migraine therapy, its use as an acute treatment can be limited by the high rate of nausea and vomiting reported by patients, which often requires pretreatment with antiemetics,” Dr. Smith and colleagues wrote. “Furthermore, IV DHE mesylate needs to be administered in emergency room settings or by headache specialists, limiting convenience.”
A novel delivery system
“There’s already a nasal spray on the market right now which doesn’t seem to work that well in a large number of people. This device [INP04] was designed to get the same substances to a part of the nose that’s higher and farther back, where there may be better absorption,” said Alan Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles, said in an interview. Dr. Rapoport was not involved with the study.
The proprietary Precision Olfactory Delivery (POD) is meant to improve on current nasal delivery methods such as sprays, droppers, and pumps, which may deliver “less than 5% of the active drug to the upper nasal space,” according to a press release from Impel NeuroPharma.
Nasal delivery also may have advantages over oral medications. People with migraines may be more likely to have gastroparesis – delayed stomach emptying – which may affect their ability to absorb oral medications and delay symptom relief. However, patients may hesitate to agree to a medication that involves nasal delivery, Dr. Rapoport said.
“I will say it’s a little more difficult getting your patients to take a nasal spray,” Dr. Rapoport said. “Patients are used to taking tablets for their headaches,” he said. “But if the doctor spends a little more time with the patient and says, ‘Look, this could work faster for your migraine as a nasal spray. Why don’t you try it a couple of times and see if you like it or not?’ patients are usually willing to give it a try.”
The study’s limitations include the lack of a control group given that it was an open-label trial. It was carried out at 38 sites in one geographical area, which may affect the generalizability of the results. The study did not assess patients with new-onset migraine or chronic migraine.
The Food and Drug Administration approved Trudhesa on Sept. 2, 2021.
The study was funded by Impel NeuroPharma. Dr. Smith has received funding from a number of pharmaceutical companies. Dr. Rapoport disclosed no relevant financial relationships.
From Headache
Virtual roller-coaster may explain the ups and downs of migraine
and may explain the mechanisms underlying common symptoms and increased activity in certain brain regions in migraine patients.
In a new study, the prevalence of dizziness was 65% among patients with migraine who underwent a virtual roller-coaster ride versus 30% among those without migraine. In addition, imaging showed greater neuronal activity after the simulation in those with migraine.
“Migraine patients reported more dizziness and motion sickness, as well as longer symptom duration and intensity, in a virtual roller-coaster ride,” even though the videos and timing were identical for both groups, said study investigator Arne May, MD, PhD, professor of neurology at the University of Hamburg (Germany).
“We found differences not just in behavioral results but also in specific activations of areas within the cerebellum and the frontal gyrus. Migraine patients process such visual input differently from controls and activate a specific brain network to do so,” he added.
The findings were published online July 21, 2021, in Neurology.
The brain’s response
Nausea, which is among the diagnostic criteria for migraine, is the main symptom of motion sickness. Vestibular symptoms such as dizziness are also components of migraine.
Previous research has examined how the brain processes visual and motion stimuli in migraine, but the reasons patients with migraine are susceptible to motion sickness and dizziness remain unclear.
The researchers used a simulated roller-coaster ride to study the clinical and brain responses to motion among participants with and participants without migraine. They enrolled 20 consecutive patients with migraine who presented to a tertiary headache clinic between January and March 2020 and enrolled 20 healthy participants from a university hospital and the community. The average age of the study population was 30 years, and more than 80% were women.
In response to a questionnaire, participants provided information about demographics and headache features, including onset, frequency, and intensity. They also provided information about their status within the migraine phase and about vestibular symptoms experienced in daily life.
While undergoing functional MRI (fMRI), all participants watched two short videos that provided a first-person perspective of a roller-coaster ride. During the videos, they wore ear buds that conveyed the sound of a car riding over the rails.
The first video included more horizontal perspectives, and the second had more vertical perspectives. Each video was shown three times in random order.
During fMRI, participants reported intensity of nausea and vestibular symptoms using an 11-point Likert scale. After the experiment, they responded to a questionnaire that evaluated intensity and duration of nausea, dizziness, and vertigo experienced during the videos.
Participants also were given the Simulator Sickness Questionnaire (SSQ), which assessed motion sickness. A 100-point visual analog scale (VAS) was used to rate how realistic the roller-coaster experience had been.
There were no differences in sex or age between the migraine group and the healthy control group. Half of the patients with migraine reported aura. The mean number of migraine attacks within the previous month was 3.7. The mean Migraine Disability Assessment score was 21.5, which indicates severe disability.
Nausea, dizziness often neglected
Baseline prevalence of vestibular symptoms was 75% in the migraine group and 5% in the control group (P < .0001). These symptoms included dizziness (60% and 5%, respectively; P < .0001) and postural symptoms (40% and 0%, respectively; P = .003).
At baseline, vestibular symptoms were more frequent (P = .001), more intense (P < .0001), and were associated with greater disability (P = .001) in patients with migraine, compared with participants without migraine. The patients with migraine were also more susceptible to motion sickness (P = .02) and had higher depression scores (P = .001).
During the roller-coaster simulation, dizziness was more prevalent among patients with migraine than among those without migraine (65% vs. 30%; P = .03). Patients with migraine also reported more motion sickness (SSQ score, 47.3 vs. 24.3; P = .004), longer symptom duration (1:19 minutes vs. 00:27 minutes; P = .03), and symptoms of greater intensity (VAS, 22.0 vs. 9.9; P = .03).
Brain activity also differed between groups. Among patients with migraine, neuronal activity was greater in clusters within the right superior and left inferior occipital gyrus, the left pontine nuclei, and the left cerebellar lobules V and VI.
There was a moderately negative correlation of activation of the inferior occipital gyrus with migraine disability (r = –0.46; P = .04). Activation within the pontine nuclei correlated positively with motion sickness scores (r = 0.32; P = .04).
In addition, among patients with migraine, activity in the cerebellar lobule VIIb and in the left middle frontal gyrus was decreased in comparison with persons without migraine. Also among patients with migraine, there was enhanced connectivity between the pontine nuclei, cerebellar areas V and VI, and the interior and superior occipital gyrus and numerous cortical areas.
Clinicians often neglect to treat dizziness and nausea in patients with migraine, said Dr. May. However, these symptoms are part of migraine, even when attacks are not occurring.
“I have learned that if we can explain such symptoms, they are better accepted,” said Dr. May. “We need more and better basic research because we need to understand before we treat.”
Toward faster, more effective treatment
Commenting on the study, Erik Viirre, MD, PhD, professor in the department of neurosciences, University of California, San Diego, said, “we can be excited and celebrate that these researchers are using these news tools to investigate the operation of the migraine brain.
“That will combine with the new therapies and the genomics to give us a powerful approach to this particular condition,” said Dr. Viirre, who was not involved with the research.
The findings provide significant detail about the interconnections between the various brain regions affected by migraine, he noted. These regions include not just the sensory centers but also areas involved in higher executive function and emotional responses.
By identifying these regions, the findings show “some of the underlying mechanisms of these clinically relevant features,” said Dr. Viirre, who is also director of UCSD’s Arthur C. Clarke Center for Human Imagination.
The investigators set up the motion simulation well and used sound fMRI methodology, he added. However, imaging studies of the brain’s response to motion pose several challenges.
“The biggest challenge in any of these circumstances is that you can’t put an actual fMRI scanner on a roller-coaster,” said Dr. Viirre. “The actual acceleration and gravitational sensations delivered by a roller-coaster and gravity, of course, do not occur when you’re lying still in an MRI scanner.” Nevertheless, the pseudoacceleration produced by a visual stimulus is a reasonable proxy.
The findings also suggest that researchers in the future could examine whether any new therapeutic interventions for migraine modulate the brain functions differently for individuals with migraine than for those without migraine, he noted.
“That’s going to lead us to a faster, more effective, more reliable suite of migraine therapies,” said Dr. Viirre.
The study also reminds clinicians to take a broader approach to patients with migraine, and it underscores the value of strategies such as self-calming techniques, which can reduce the number and intensity of headaches, he said.
“Literally demonstrating these functional differences in the migraine brain is a hugely important message of advocacy for people with migraine,” Dr. Viirre concluded.
The study was funded by the German Research Foundation. Drs. May and Viirre have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
and may explain the mechanisms underlying common symptoms and increased activity in certain brain regions in migraine patients.
In a new study, the prevalence of dizziness was 65% among patients with migraine who underwent a virtual roller-coaster ride versus 30% among those without migraine. In addition, imaging showed greater neuronal activity after the simulation in those with migraine.
“Migraine patients reported more dizziness and motion sickness, as well as longer symptom duration and intensity, in a virtual roller-coaster ride,” even though the videos and timing were identical for both groups, said study investigator Arne May, MD, PhD, professor of neurology at the University of Hamburg (Germany).
“We found differences not just in behavioral results but also in specific activations of areas within the cerebellum and the frontal gyrus. Migraine patients process such visual input differently from controls and activate a specific brain network to do so,” he added.
The findings were published online July 21, 2021, in Neurology.
The brain’s response
Nausea, which is among the diagnostic criteria for migraine, is the main symptom of motion sickness. Vestibular symptoms such as dizziness are also components of migraine.
Previous research has examined how the brain processes visual and motion stimuli in migraine, but the reasons patients with migraine are susceptible to motion sickness and dizziness remain unclear.
The researchers used a simulated roller-coaster ride to study the clinical and brain responses to motion among participants with and participants without migraine. They enrolled 20 consecutive patients with migraine who presented to a tertiary headache clinic between January and March 2020 and enrolled 20 healthy participants from a university hospital and the community. The average age of the study population was 30 years, and more than 80% were women.
In response to a questionnaire, participants provided information about demographics and headache features, including onset, frequency, and intensity. They also provided information about their status within the migraine phase and about vestibular symptoms experienced in daily life.
While undergoing functional MRI (fMRI), all participants watched two short videos that provided a first-person perspective of a roller-coaster ride. During the videos, they wore ear buds that conveyed the sound of a car riding over the rails.
The first video included more horizontal perspectives, and the second had more vertical perspectives. Each video was shown three times in random order.
During fMRI, participants reported intensity of nausea and vestibular symptoms using an 11-point Likert scale. After the experiment, they responded to a questionnaire that evaluated intensity and duration of nausea, dizziness, and vertigo experienced during the videos.
Participants also were given the Simulator Sickness Questionnaire (SSQ), which assessed motion sickness. A 100-point visual analog scale (VAS) was used to rate how realistic the roller-coaster experience had been.
There were no differences in sex or age between the migraine group and the healthy control group. Half of the patients with migraine reported aura. The mean number of migraine attacks within the previous month was 3.7. The mean Migraine Disability Assessment score was 21.5, which indicates severe disability.
Nausea, dizziness often neglected
Baseline prevalence of vestibular symptoms was 75% in the migraine group and 5% in the control group (P < .0001). These symptoms included dizziness (60% and 5%, respectively; P < .0001) and postural symptoms (40% and 0%, respectively; P = .003).
At baseline, vestibular symptoms were more frequent (P = .001), more intense (P < .0001), and were associated with greater disability (P = .001) in patients with migraine, compared with participants without migraine. The patients with migraine were also more susceptible to motion sickness (P = .02) and had higher depression scores (P = .001).
During the roller-coaster simulation, dizziness was more prevalent among patients with migraine than among those without migraine (65% vs. 30%; P = .03). Patients with migraine also reported more motion sickness (SSQ score, 47.3 vs. 24.3; P = .004), longer symptom duration (1:19 minutes vs. 00:27 minutes; P = .03), and symptoms of greater intensity (VAS, 22.0 vs. 9.9; P = .03).
Brain activity also differed between groups. Among patients with migraine, neuronal activity was greater in clusters within the right superior and left inferior occipital gyrus, the left pontine nuclei, and the left cerebellar lobules V and VI.
There was a moderately negative correlation of activation of the inferior occipital gyrus with migraine disability (r = –0.46; P = .04). Activation within the pontine nuclei correlated positively with motion sickness scores (r = 0.32; P = .04).
In addition, among patients with migraine, activity in the cerebellar lobule VIIb and in the left middle frontal gyrus was decreased in comparison with persons without migraine. Also among patients with migraine, there was enhanced connectivity between the pontine nuclei, cerebellar areas V and VI, and the interior and superior occipital gyrus and numerous cortical areas.
Clinicians often neglect to treat dizziness and nausea in patients with migraine, said Dr. May. However, these symptoms are part of migraine, even when attacks are not occurring.
“I have learned that if we can explain such symptoms, they are better accepted,” said Dr. May. “We need more and better basic research because we need to understand before we treat.”
Toward faster, more effective treatment
Commenting on the study, Erik Viirre, MD, PhD, professor in the department of neurosciences, University of California, San Diego, said, “we can be excited and celebrate that these researchers are using these news tools to investigate the operation of the migraine brain.
“That will combine with the new therapies and the genomics to give us a powerful approach to this particular condition,” said Dr. Viirre, who was not involved with the research.
The findings provide significant detail about the interconnections between the various brain regions affected by migraine, he noted. These regions include not just the sensory centers but also areas involved in higher executive function and emotional responses.
By identifying these regions, the findings show “some of the underlying mechanisms of these clinically relevant features,” said Dr. Viirre, who is also director of UCSD’s Arthur C. Clarke Center for Human Imagination.
The investigators set up the motion simulation well and used sound fMRI methodology, he added. However, imaging studies of the brain’s response to motion pose several challenges.
“The biggest challenge in any of these circumstances is that you can’t put an actual fMRI scanner on a roller-coaster,” said Dr. Viirre. “The actual acceleration and gravitational sensations delivered by a roller-coaster and gravity, of course, do not occur when you’re lying still in an MRI scanner.” Nevertheless, the pseudoacceleration produced by a visual stimulus is a reasonable proxy.
The findings also suggest that researchers in the future could examine whether any new therapeutic interventions for migraine modulate the brain functions differently for individuals with migraine than for those without migraine, he noted.
“That’s going to lead us to a faster, more effective, more reliable suite of migraine therapies,” said Dr. Viirre.
The study also reminds clinicians to take a broader approach to patients with migraine, and it underscores the value of strategies such as self-calming techniques, which can reduce the number and intensity of headaches, he said.
“Literally demonstrating these functional differences in the migraine brain is a hugely important message of advocacy for people with migraine,” Dr. Viirre concluded.
The study was funded by the German Research Foundation. Drs. May and Viirre have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
and may explain the mechanisms underlying common symptoms and increased activity in certain brain regions in migraine patients.
In a new study, the prevalence of dizziness was 65% among patients with migraine who underwent a virtual roller-coaster ride versus 30% among those without migraine. In addition, imaging showed greater neuronal activity after the simulation in those with migraine.
“Migraine patients reported more dizziness and motion sickness, as well as longer symptom duration and intensity, in a virtual roller-coaster ride,” even though the videos and timing were identical for both groups, said study investigator Arne May, MD, PhD, professor of neurology at the University of Hamburg (Germany).
“We found differences not just in behavioral results but also in specific activations of areas within the cerebellum and the frontal gyrus. Migraine patients process such visual input differently from controls and activate a specific brain network to do so,” he added.
The findings were published online July 21, 2021, in Neurology.
The brain’s response
Nausea, which is among the diagnostic criteria for migraine, is the main symptom of motion sickness. Vestibular symptoms such as dizziness are also components of migraine.
Previous research has examined how the brain processes visual and motion stimuli in migraine, but the reasons patients with migraine are susceptible to motion sickness and dizziness remain unclear.
The researchers used a simulated roller-coaster ride to study the clinical and brain responses to motion among participants with and participants without migraine. They enrolled 20 consecutive patients with migraine who presented to a tertiary headache clinic between January and March 2020 and enrolled 20 healthy participants from a university hospital and the community. The average age of the study population was 30 years, and more than 80% were women.
In response to a questionnaire, participants provided information about demographics and headache features, including onset, frequency, and intensity. They also provided information about their status within the migraine phase and about vestibular symptoms experienced in daily life.
While undergoing functional MRI (fMRI), all participants watched two short videos that provided a first-person perspective of a roller-coaster ride. During the videos, they wore ear buds that conveyed the sound of a car riding over the rails.
The first video included more horizontal perspectives, and the second had more vertical perspectives. Each video was shown three times in random order.
During fMRI, participants reported intensity of nausea and vestibular symptoms using an 11-point Likert scale. After the experiment, they responded to a questionnaire that evaluated intensity and duration of nausea, dizziness, and vertigo experienced during the videos.
Participants also were given the Simulator Sickness Questionnaire (SSQ), which assessed motion sickness. A 100-point visual analog scale (VAS) was used to rate how realistic the roller-coaster experience had been.
There were no differences in sex or age between the migraine group and the healthy control group. Half of the patients with migraine reported aura. The mean number of migraine attacks within the previous month was 3.7. The mean Migraine Disability Assessment score was 21.5, which indicates severe disability.
Nausea, dizziness often neglected
Baseline prevalence of vestibular symptoms was 75% in the migraine group and 5% in the control group (P < .0001). These symptoms included dizziness (60% and 5%, respectively; P < .0001) and postural symptoms (40% and 0%, respectively; P = .003).
At baseline, vestibular symptoms were more frequent (P = .001), more intense (P < .0001), and were associated with greater disability (P = .001) in patients with migraine, compared with participants without migraine. The patients with migraine were also more susceptible to motion sickness (P = .02) and had higher depression scores (P = .001).
During the roller-coaster simulation, dizziness was more prevalent among patients with migraine than among those without migraine (65% vs. 30%; P = .03). Patients with migraine also reported more motion sickness (SSQ score, 47.3 vs. 24.3; P = .004), longer symptom duration (1:19 minutes vs. 00:27 minutes; P = .03), and symptoms of greater intensity (VAS, 22.0 vs. 9.9; P = .03).
Brain activity also differed between groups. Among patients with migraine, neuronal activity was greater in clusters within the right superior and left inferior occipital gyrus, the left pontine nuclei, and the left cerebellar lobules V and VI.
There was a moderately negative correlation of activation of the inferior occipital gyrus with migraine disability (r = –0.46; P = .04). Activation within the pontine nuclei correlated positively with motion sickness scores (r = 0.32; P = .04).
In addition, among patients with migraine, activity in the cerebellar lobule VIIb and in the left middle frontal gyrus was decreased in comparison with persons without migraine. Also among patients with migraine, there was enhanced connectivity between the pontine nuclei, cerebellar areas V and VI, and the interior and superior occipital gyrus and numerous cortical areas.
Clinicians often neglect to treat dizziness and nausea in patients with migraine, said Dr. May. However, these symptoms are part of migraine, even when attacks are not occurring.
“I have learned that if we can explain such symptoms, they are better accepted,” said Dr. May. “We need more and better basic research because we need to understand before we treat.”
Toward faster, more effective treatment
Commenting on the study, Erik Viirre, MD, PhD, professor in the department of neurosciences, University of California, San Diego, said, “we can be excited and celebrate that these researchers are using these news tools to investigate the operation of the migraine brain.
“That will combine with the new therapies and the genomics to give us a powerful approach to this particular condition,” said Dr. Viirre, who was not involved with the research.
The findings provide significant detail about the interconnections between the various brain regions affected by migraine, he noted. These regions include not just the sensory centers but also areas involved in higher executive function and emotional responses.
By identifying these regions, the findings show “some of the underlying mechanisms of these clinically relevant features,” said Dr. Viirre, who is also director of UCSD’s Arthur C. Clarke Center for Human Imagination.
The investigators set up the motion simulation well and used sound fMRI methodology, he added. However, imaging studies of the brain’s response to motion pose several challenges.
“The biggest challenge in any of these circumstances is that you can’t put an actual fMRI scanner on a roller-coaster,” said Dr. Viirre. “The actual acceleration and gravitational sensations delivered by a roller-coaster and gravity, of course, do not occur when you’re lying still in an MRI scanner.” Nevertheless, the pseudoacceleration produced by a visual stimulus is a reasonable proxy.
The findings also suggest that researchers in the future could examine whether any new therapeutic interventions for migraine modulate the brain functions differently for individuals with migraine than for those without migraine, he noted.
“That’s going to lead us to a faster, more effective, more reliable suite of migraine therapies,” said Dr. Viirre.
The study also reminds clinicians to take a broader approach to patients with migraine, and it underscores the value of strategies such as self-calming techniques, which can reduce the number and intensity of headaches, he said.
“Literally demonstrating these functional differences in the migraine brain is a hugely important message of advocacy for people with migraine,” Dr. Viirre concluded.
The study was funded by the German Research Foundation. Drs. May and Viirre have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.